1 Receptors Localisation: in membrame, in cytosol, in nuclei, in mitochondria Receptor transform information from our sense to biological signals = electrical Action Potential 2 Type of receptors for senses ¨Photoreceptors (rod and cone) ¨Mechanoreceptors (touch on the skin, sound wave detection, wave detection in inner ear) ¨Chemoreceptors (detection of molecules in food) ¨Termoreceptors nCold 23-28 nWarm 38-43 nFast chang…0.1 gradius nSlow change….bigger difference 3 ¨Physiology of vision 4 ¨Functional anatomy of the eye ¤Optical ¤Neural ¨Photoreceptors ¤Rods ¤Cones ¨Phototransduction ¤Mechanism ¤Termination ¤Light adaptation ¨Colour Vision ¤ ¨ ¨ ¨ ¨ ¨ 5 The auditory system is one of the engineering masterpieces of the human body. At the heart of the system is an array of miniature acoustical detectors packed into a space no larger than a pea. These detectors can faithfully transduce vibrations as small as the diameter of an atom, and they can respond a thousand times faster than visual photoreceptors. Such rapid auditory responses to acoustical cues facilitate the initial orientation of the head and body to novel stimuli, especially those that are not initially within the field of view. Although humans are highly visual creatures, much human communication is mediated by the auditory system; indeed, loss of hearing can be more socially debilitating than blindness. From a cultural perspective, the auditory system is essential not only to language, but also to music, one of the most aesthetically sophisticated forms of human expression. For these and other reasons, audition represents a fascinating and especially important aspect of sensation, and more generally of brain function. Optical anatomy of the eye 6 ¨Optical portion of eye focuses ¨light thru cornea and lens onto ¨the fovea. ¨Cornea ¤Thin, transparent epithelium devoid of blood vessels ¤Receives nutrients by diffusion from tear fluid ¤Major refraktory portion of the eya, has unmyelinated nerve endings sensitive to touch and pressure ¤Aqueous humor ¤Produced by ciliary epithelial cells. Protein free watery liquid that supplies nutrients to cornea and lens ¤Maintains intraocular pressure and gives shape to anterior portion of eye ¤ ¤ http://www.studentconsult.com/common/showimage.cfm?mediaISBN=0721632564&FigFile=S23283-013-f006a.jp g&size=fullsize Boron, Boulpaep: Medical Physiology, 2003 Cornea: major refractory portion of the eye (fixed refractory index). Has unmyelinated nerve endings sensitive to touch and pressure. Receives nutrients thru diffusion from tear fluid. Laser eye surgery reshapes the cornea to reduce the need for corrective lenses. Aqueous humor: produced by ciliary epithelial cells. High rate of turnover. Gluacoma increases pressure in eye due to increased production or decreased drainage. Canals of Schlemm drain the aqeuous humor. The eye is a fluid-filled sphere enclosed by three layers of tissue (Figure 11.1). Most of the outer layer is composed of a tough white fibrous tissue, the sclera. At the front of the eye, however, this opaque outer layer is transformed into the cornea, a specialized transparent tissue that permits light rays to enter the eye. The middle layer of tissue includes three distinct but continuous structures: the iris, the ciliary body, and the choroid. The iris is the colored portion of the eye that can be seen through the cornea. It contains two sets of muscles with opposing actions, which allow the size of the pupil (the opening in its center) to be adjusted under neural control. The ciliary body is a ring of tissue that encircles the lens and includes a muscular component that is important for adjusting the refractive power of the lens, and a vascular component (the so-called ciliary processes) that produces the fluid that fills the front of the eye. The choroid is composed of a rich capillary bed that serves as the main source of blood supply for the photoreceptors of the retina. Only the innermost layer of the eye, the retina, contains neurons that are sensitive to light and are capable of transmitting visual signals to central targets. En route to the retina, light passes through the cornea, the lens, and two distinct fluid environments. The anterior chamber, the space between the lens and the cornea, is filled with aqueous humor, a clear, watery liquid that supplies nutrients to these structures as well as to the lens. Aqueous humor is produced by the ciliary processes in the posterior chamber (the region between the lens and the iris) and flows into the anterior chamber through the pupil. A specialized meshwork of cells that lies at the junction of the iris and the cornea is responsible for its uptake. Under normal conditions, the rates of aqueous humor production and uptake are in equilibrium, ensuring a constant intraocular pressure. Abnormally high levels of intraocular pressure, which occur in glaucoma, can reduce the blood supply to the eye and eventually damage retinal neurons. The space between the back of the lens and the surface of the retina is filled with a thick, gelatinous substance called the vitreous humor, which accounts for about 80% of the volume of the eye. In addition to maintaining the shape of the eye, the vitreous humor contains phagocytic cells that remove blood and other debris that might otherwise interfere with light transmission. The housekeeping abilities of the vitreous humor are limited, however, as a large number of middle-aged and elderly individuals with vitreal “floaters” will attest. Floaters are collections of debris too large for phagocytic consumption that therefore remain to cast annoying shadows on the retina; they typically arise when the aging vitreous membrane pulls away from the overly long eyeball of myopic individuals. http://www.studentconsult.com/common/showimage.cfm?mediaISBN=0721632564&FigFile=S23283-013-f006a.jp g&size=fullsize Optical anatomy of the eye 7 ¨Pupil ¤Aperture of the eye ¨Iris ¤is the colored portion of the eye, than can be seen through the cornea ¤contains two sets of muscles ¤Controls diameter of pupil nContraction of sphincter muscles à miosis nContraction of radial muscles à mydriasis n ¤ ¤ http://www.vision-and-eye-health.com/images/IrisMuscles.jpg The eye is a fluid-filled sphere enclosed by three layers of tissue (Figure 11.1). Most of the outer layer is composed of a tough white fibrous tissue, the sclera. At the front of the eye, however, this opaque outer layer is transformed into the cornea, a specialized transparent tissue that permits light rays to enter the eye. The middle layer of tissue includes three distinct but continuous structures: the iris, the ciliary body, and the choroid. The iris is the colored portion of the eye that can be seen through the cornea. It contains two sets of muscles with opposing actions, which allow the size of the pupil (the opening in its center) to be adjusted under neural control. The ciliary body is a ring of tissue that encircles the lens and includes a muscular component that is important for adjusting the refractive power of the lens, and a vascular component (the so-called ciliary processes) that produces the fluid that fills the front of the eye. The choroid is composed of a rich capillary bed that serves as the main source of blood supply for the photoreceptors of the retina. Only the innermost layer of the eye, the retina, contains neurons that are sensitive to light and are capable of transmitting visual signals to central targets. En route to the retina, light passes through the cornea, the lens, and two distinct fluid environments. The anterior chamber, the space between the lens and the cornea, is filled with aqueous humor, a clear, watery liquid that supplies nutrients to these structures as well as to the lens. Aqueous humor is produced by the ciliary processes in the posterior chamber (the region between the lens and the iris) and flows into the anterior chamber through the pupil. A specialized meshwork of cells that lies at the junction of the iris and the cornea is responsible for its uptake. Under normal conditions, the rates of aqueous humor production and uptake are in equilibrium, ensuring a constant intraocular pressure. Abnormally high levels of intraocular pressure, which occur in glaucoma, can reduce the blood supply to the eye and eventually damage retinal neurons. The space between the back of the lens and the surface of the retina is filled with a thick, gelatinous substance called the vitreous humor, which accounts for about 80% of the volume of the eye. In addition to maintaining the shape of the eye, the vitreous humor contains phagocytic cells that remove blood and other debris that might otherwise interfere with light transmission. The housekeeping abilities of the vitreous humor are limited, however, as a large number of middle-aged and elderly individuals with vitreal “floaters” will attest. Floaters are collections of debris too large for phagocytic consumption that therefore remain to cast annoying shadows on the retina; they typically arise when the aging vitreous membrane pulls away from the overly long eyeball of myopic individuals. http://www.studentconsult.com/common/showimage.cfm?mediaISBN=0721632564&FigFile=S23283-013-f006a.jp g&size=fullsize Optical anatomy of the eye 8 ¨Lens ¤Dense, high protein structure that adjusts optical focus ¤Focus adjusted by process called accommodation nAt rest, zonal fibers suspend lens and keep it flat nFocus on objects far away nContraction of ciliary muscles releases tension in zonal fibers nLens becomes rounder nFocus on near objects n ¤ ¤ The eye is a fluid-filled sphere enclosed by three layers of tissue (Figure 11.1). Most of the outer layer is composed of a tough white fibrous tissue, the sclera. At the front of the eye, however, this opaque outer layer is transformed into the cornea, a specialized transparent tissue that permits light rays to enter the eye. The middle layer of tissue includes three distinct but continuous structures: the iris, the ciliary body, and the choroid. The iris is the colored portion of the eye that can be seen through the cornea. It contains two sets of muscles with opposing actions, which allow the size of the pupil (the opening in its center) to be adjusted under neural control. The ciliary body is a ring of tissue that encircles the lens and includes a muscular component that is important for adjusting the refractive power of the lens, and a vascular component (the so-called ciliary processes) that produces the fluid that fills the front of the eye. The choroid is composed of a rich capillary bed that serves as the main source of blood supply for the photoreceptors of the retina. Only the innermost layer of the eye, the retina, contains neurons that are sensitive to light and are capable of transmitting visual signals to central targets. En route to the retina, light passes through the cornea, the lens, and two distinct fluid environments. The anterior chamber, the space between the lens and the cornea, is filled with aqueous humor, a clear, watery liquid that supplies nutrients to these structures as well as to the lens. Aqueous humor is produced by the ciliary processes in the posterior chamber (the region between the lens and the iris) and flows into the anterior chamber through the pupil. A specialized meshwork of cells that lies at the junction of the iris and the cornea is responsible for its uptake. Under normal conditions, the rates of aqueous humor production and uptake are in equilibrium, ensuring a constant intraocular pressure. Abnormally high levels of intraocular pressure, which occur in glaucoma, can reduce the blood supply to the eye and eventually damage retinal neurons. The space between the back of the lens and the surface of the retina is filled with a thick, gelatinous substance called the vitreous humor, which accounts for about 80% of the volume of the eye. In addition to maintaining the shape of the eye, the vitreous humor contains phagocytic cells that remove blood and other debris that might otherwise interfere with light transmission. The housekeeping abilities of the vitreous humor are limited, however, as a large number of middle-aged and elderly individuals with vitreal “floaters” will attest. Floaters are collections of debris too large for phagocytic consumption that therefore remain to cast annoying shadows on the retina; they typically arise when the aging vitreous membrane pulls away from the overly long eyeball of myopic individuals. 9 10 Accommodation and associated disorders 11 ¨Accommodation of the lens is limited and age dependent ¨With age, lens becomes stiffer and less compliant. ¨Age related loss of accommodation called presbyopia ¨Accommodation accompanied by adaptive changes in size of pupil ¨ n ¤ ¤ 12 cataract 13 glaucoma Accommodation and associated disorders 14 ¨Myopia ¨Image focused in front of retina ¨Far away objects appear blurry ¨Hyperopia ¨Image focused behind retina ¨Close objects appear blurry Each can be caused by abnormal shape of the eye as well. ¤ ¤ http://www.mezzmer.com/blog/wp-content/uploads/2011/07/myopia.jpg Myopia: lens is too round Hyperopia: lens is too flat Astigmatism is abnormal curvature of cornea, images are blurry both near and far. Myopia and hyperopia can be caused by abnormal shape of eyeball as well. Eye that is longer than normal results in myopia, corrected with a concave lens (focuses images at longer distance) http://www.studentconsult.com/common/showimage.cfm?mediaISBN=0721632564&FigFile=S23283-013-f006a.jp g&size=fullsize Optical anatomy of the eye 15 ¨Vitreous humor ¤Gel of extracellular fluid containing collagen ¨Choroid ¤rich in blood vessels and supports the retina ¨Retina ¤Neural portion that transduces light into electrical signals that pass down the optic nerve ¤Optic nerve exits at optic disc. Devoid of photoreceptors: blind spot ¤Fovea is point on retina that has maximal visual acuity ¤ ¤ n ¤ ¤ Retina is part of the CNS derived from diencephalon Macula is yellow region at back of eye on retina. Contains fovea is broader region responsible for central vision ¨Pigment epithelium ¨Absorps light rays, prevention the reflection of rays back through the retina ¤Contains melanin to absorbs excess light ¤Stores Vitamin A ¨Photoreceptors ¤Transduce light energy into electrical energy ¤Rods and cones ¨Ganglion cells ¤Output cells of retina project via optic nerve ¤Bipolar cells – 12 different types occur ¤Horizontal cells ¤Amacrine cells - 29types have been described ¤The neural elements of retina are bound together by glial cells – Muller cells ¨ ¤ http://www.studentconsult.com/common/showimage.cfm?mediaISBN=0721632564&FigFile=S23283-013-f007.jpg &size=fullsize Boron, Boulpaep, Medical Physiology, 2003 RETINA Its organized on layers Visual receptors+4types of neurons. Many different synaptic transmitters Inner segments Despite its peripheral location, the retina or neural portion of the eye, is actually part of the central nervous system. There are five types of neurons in the retina: photoreceptors, bipolar cells, ganglion cells, horizontal cells, and amacrine cells. Absorption of light by the photopigment in the outer segment of the photoreceptors initiates a cascade of events that changes the membrane potential of the receptor, and therefore the amount of neurotransmitter released by the photoreceptor synapses onto the cells they contact. At first glance, the spatial arrangement of retinal layers seems counterintuitive, since light rays must pass through the non-light-sensitive elements of the retina (and retinal vasculature!) before reaching the outer segments of the photoreceptors, where photons are absorbed. The reason for this curious feature of retinal organization lies in the special relationship that exists between the outer segments of the photoreceptors and the pigment epithelium. The outer segments contain membranous disks that house the light-sensitive photopigment and other proteins involved in the transduction process. These disks are formed near the inner segment of the photoreceptor and move toward the tip of the outer segment, where they are shed. The pigment epithelium plays an essential role in removing the expended receptor disks; this is no small task, since all the disks in the outer segments are replaced every 12 days. In addition, the pigment epithelium contains the biochemical machinery that is required to regenerate photopigment molecules after they have been exposed to light. It is presumably the demands of the photoreceptor disk life cycle and photopigment recycling that explain why rods and cones are found in the outermost rather than the innermost layer of the retina. Disruptions in the normal relationships between pigment epithelium and retinal photoreceptors such as those that occur in retinitis pigmentosa have severe consequences for vision 17 ¨Periphery of retina ¨High degree of convergence à large receptive field ¨High sensitivity to light, low spatial resolution ¨Fovea ¨Low convergence à small receptive fields ¨Lower sensitivity to light, high resolution (visual acuity) http://www.studentconsult.com/common/showimage.cfm?mediaISBN=0721632564&FigFile=S23283-013-f008.jpg &size=fullsize At the periphery of the retina there is convergence of synaptic input from many photoreceptors onto bipolar and ganglion cells, reducing spatial resolution because receptive fields are larger, but increasing sensitivity because more photoreceptors collect light Outside fovea density of cones drops and density of rods rises; there are no photoreceptors at optic disc where ganglion cell axons leave retina (blind spot). Fovea is region 300-700 m in diameter located in center of retina and contains the highest density of cones Over most of retina, light must travel through several layers to reach photoreceptors; at fovea layers of neurons are shifted aside, reducing distortion due to light scatter Most photoreceptors in fovea synapse on only one bipolar cell which in turn synapses on only one ganglion cell, resulting in smallest receptive fields and greatest resolution Fovea 18 E:\306\images\blks 6th ed\images\008004.jpg Visual acuity of fovea enhanced by: ¨One to one ratio of photoreceptor to ganglion cell ¨Lateral displacement of neurons to minimize scattering of light ¨High density of cones Cones are narrower and can pack more densley Photoreceptors 19 Rods ¨Responsible for monochromatic, dark- adapted vision ¨Inner segment contains nucleus and metabolic machinery ¨Produces photopigment ¨Outer segments is transduction site ¨Consists of high density of stacks of disk membranes: flattened, membrane bound organelles ¨contain the photopigment rhodopsin v v http://www.studentconsult.com/common/showimage.cfm?mediaISBN=0721632564&FigFile=S23283-013-f007.jpg &size=fullsize http://www.studentconsult.com/common/showimage.cfm?mediaISBN=0721632564&FigFile=S23283-013-f007.jpg &size=fullsize Photoreceptors consist of synaptic terminal connected by short axon to inner segment (contains nucleus and metabolic machinery) and outer segment. Outer segments of rods consist of stacks of membrane discs rich in photopigment rhodopsin. Inner segment synthesizes photopigments and inserts them into membrane of vesicles which move from inner to outer segment. In rods vesicles become incorporated into new discs, which move up the stack until they reach apex where they are shed and recycled by pigment epithelium. Photoreceptors 20 ¨Cones ¨3 subtypes responsible for colour vision ¨Inner segment produces photopigments similar to rhodopsin ¨Outer segments is transduction site ¤consist of infolded stack membranes that are continuous with the outer membrane nvesicles containing pigment are inserted into the membrane folds of the outer segment Photopigments contain same retinal, just different forms of opsin Outer segments of cones consist of folded, stacked membrane containing other photopigments (opsins) but in lower concentration than rods therefore less sensitive to light. As with rods, the inner segment synthesizes photopigments and inserts them into membrane of vesicles which move from inner to outer segment. However, in cones the vesicles are inserted into membrane folds of outer segment Phototransduction: Dark current 21 ¨Partially active guanylyl cyclase keeps cytoplasmic [cGMP] high in the dark ¨Outer segment contains cGMP-gated cation channels ¤Influx of Na+ and Ca2+ ¨Inner segment contains non-gated K+ selective channels ¤K+ efflux ¨Resting, or dark Vm is -40 mV ¨concentration gradients maintained by Na+/K+ pump and NCX ¨ Guanylyl cyclase synthesizes cGMP from GTP Outer segment membrane has cation channels which remain open in the dark whereas inner segment has K+ channels that are not regulated by light. Na+ (90%) and Ca++(10%) enter through cation channels in outer segment and K+ leaves inner segment, resulting in hyperpolarization (resting membrane potential of rods is ~ – 40 mV ) and ionic current called dark current. Na-K pump removes Na+ from inner segment and Na-Ca exchanger removes Ca++ from outer segment to maintain concentration gradients. 22 Phototransduction 23 ¨Photoreceptors hyperpolarize in response to light and release less neurotransmitter ¨In darkness, the Vm of -40 mV keeps CaV channels in the synaptic terminal open ¤photoreceptors continuously release neurotransmitter glutamate ¨absorption of light by photopigment ò’s [cGMP] ¤cation channels close ¤K+ efflux predominates, hyperpolarizes cell (-70mV) ¤CaV channels close, decreased release of glutamate ¨ Depolarized state of membrane keeps voltage-gated Ca++ channels open in synaptic terminals, resulting in constant release of neurotransmitter (glutamate) http://www.studentconsult.com/common/showimage.cfm?mediaISBN=0721632564&FigFile=S23283-013-f011b.jp g&size=fullsize Phototransduction: mechanism 24 ¨Photopigment rhodopsin is the light receptor in rods ¤opsin nG-protein coupled membrane receptor ¤Retinal= retinene1 nLight absorbing compound nthe aldehyde nform of retinol or nVitamin A ¨ B&B Figure 13-11 rhodopsin ¨retinal changes conformation from 11-cis to all-trans after absorbing a photon ¨isomerization of retinal activates opsin opsin Aldehyde is r-c=o Retinol contains only an C-OH Trans form is more stable ¨ 25 Phototransduction: mechanism 26 1.Absorption of a photon isomerizes retinal a)Converts opsin to metarhodopsin II 2.Metarodophsin II activates the G-protein transducin a)Activates cGMP phosphodiesterase (PDE) 3.PDE hydrolyzes cGMP to GMP a)Decreased [cGMP] closes cGMP gated cation channels b)Photoreceptor hyperpolarizes, less glutamate released 4. 4. 4. 4. light transducin exchanges GDP for GTP activated transducin (G protein) → activates cGMP phosphodiesterase → hydrolyzes cGMP to GMP (5’-guanylate monophosphate)→ ↓ [cGMP]i → closes cGMP-gated cation channels → hyperpolarization → ↓ neurotransmitter release all-trans retinal separates from opsin (bleaching) converts to retinol translocates to the pigment epithelium where it is converted back to 11-cis retinal returns to the outer segment and recombines with opsin recycling process takes several minutes Phototransduction: termination 27 ¨Activated rhodopsin is a target for phosphorylation by rhodopsin kinase ¤Phosphorylated rhodopsin inactivated by cytosolic protein arrestin ¨All-trans retinal transported to the pigment epithelium where it is converted back to 11-cis retinal, and recycled back to the rod ¨Activated transducin inactivates itself by hydrolyzing GTP to GDP ¨ Ca++ entry through cation channels inhibits guanylyl cyclase, which synthesizes cGMP, and stimulates phosphodiesterase to regulate [cGMP]I closure of cGMP-gated channels → ↓ [Ca++]i, reducing inhibition of guanylyl cyclase and inhibiting phosphodiesterase to increase [cGMP]i Phototransduction: light adaptation 28 ¨Eyes adapt to increased light intensity and remain sensitive to further changes in light qOptic adaptation: qConstriction of pupils to allow in less light qPhotoreceptor adaptation: qThe closure of cGMP gated channel reduces inward flux of Ca2+ àdecreased [Ca2+]i qCa2+ induced inhibition of guanylyl cyclase removed qMore cGMP made à reopening of some cGMP gated channels à influx of cations à slight depolarization ¨Photoreceptor can once again be stimulated (hyperpolarized) by photons q ¨ Ca++ entry through cation channels inhibits guanylyl cyclase, which synthesizes cGMP, and stimulates phosphodiesterase to regulate [cGMP]I closure of cGMP-gated channels → ↓ [Ca++]i, reducing inhibition of guanylyl cyclase and inhibiting phosphodiesterase to increase [cGMP]i Colour Vision 29 q3 types of cones, each contain photopigment with different absorption spectra q420 nm – blue q530 nm – green q560 nm - red qColour interpreted by ratio of cone stimulation qOrange (580nm) light stimulates: qBlue cone – 0% qGreen cone – 42% qRed cone – 99% q0:42:99 ratio of cone stimulation interpreted by brain as orange Guyton Figure 50-8 Rod Cones actually respond to violet, yellow-green, and yellow-red but called blue green red by convention Rod peak wavelength at 500nm Red green colour blindness: red or green cones missing, therefore cannot distinguish red from green because the colour spectra overlap. Colour Vision: Disorders 30 ¨Malfunction of one group of cones leads to colour blindness ¨Most common form is red-green colour blindness ¤Either red or green cones are missing ¤Difficulty distinguishing red from green because the colour spectra overlap (ratio of cone stimulation is affected à impaired neural interpretation of colours) File:Ishihara 9.png The spots are arranged so that a normal vision person sees a 74, whereas a red-green colour blind person sees a 21 31 Retinal circuitry: review of cell types 32 ¨rods and cones synapse on bipolar cells and horizontal cells ¨horizontal cells make lateral inhibitory synapses with surrounding bipolar cells or photoreceptors ¨bipolar cells make synaptic connections with ganglion cells and amacrine cells ¨amacrine cells transmit signals from bipolar cells to ganglion cells or to other amacrine cells ¨ganglion cells transmit action potentials to the brain via the optic nerve B&L Figure 8-7 Interplexiform cells: transmit signals in the retrograde manner from the inner plexiform layer to the outer plexiform layer. Signals are inhibitory and control lateral spread of visual signals by horizontal cells in the outer plexifrom layer. Role may be to help control the degree of contrast in the visual image. Amacrine cells help analyze visual signals before they leave the retina. There are two type of bipolar cells: •“on type” have excitatory receptors •“off-type” have inhibitory receptors Amacrine cells: •transform sustained bipolar cell output into transient responses of ganglion cells •act as interneurons in pathway from rod bipolar cells to ganglion cells Retinal circuitry: key features 33 ¨2 types of bipolar cells ¨On center: hyperpolarized by glutamate ¨Off center: depolarized by glutamate ¨Bipolar and horizontal cells play a role in lateral inhibition ¨ Important for increasing visual contrast ¨Set up “surround” arrangement of ganglion cell receptive fields http://www.studentconsult.com/common/showimage.cfm?mediaISBN=9780323045827&FigFile=M9780323045827-0 08-f007.jpg&size=fullsize B&L Figure 8-7 Direct path: Photoreceptor  bipolar cell  ganglion cell Indirect path: Photoreceptor  horizontal, amacrine, bipolar cells  ganglion cells cones in center of ganglion cell receptive field influence ganglion cell activity by direct pathway cones in surround of ganglion cell receptive field influence ganglion cell activity by indirect pathway Receptive fields 34 ¨Photoreceptor receptive fields include retinal area that, when stimulated by light, results in hyperpolarization of individual photoreceptor ¤Small and circular ¨Ganglion cell receptive field size determined by ¤ganglion cell type ¤degree of convergence of photoreceptors and bipolar cells ¨ and field type by retinal circuitry (lateral inhibition) nOn-center/off-surround nOff-center/on-surround Where in the retina is there is there a high degree of convergence? i.e., response in center of receptive field is opposite to response in surround, due to opposite effects of direct and lateral pathways depolarized by glutamate (opening of Na+ channels) hyperpolarized by glutamate (opening of K+ channels or closing of Na+ channels) Receptive fields 35 ¨On-center/off-surround ¤Light shines on center of ganglion cell receptive field à ganglion cell increases AP firing ¤Light on surround region à decreased AP firing ¨Off-center/on-surround ¤Light on center à decreased AP firing ¤Light on surround à increased AP firing ¤ C:\Users\Felix\Documents\KIN 306\JPEGs\images\008008B.jpg C:\Users\Felix\Documents\KIN 306\JPEGs\images\008008G.jpg B&L Figure 8-8 Always have a tonic release of AP, but their frequency is mediated by center/surround receptive fields Neural circuits of retinal receptive fields 36 centre surround surround Ganglion cell receptive field P P P B B G G H H _ _ On-center bipolar and ganglion cells Off-center bipolar and ganglion cells On center bipolar cells hyperpolarized by glutamate Off center bipolar cells depolarized by glutamate Center photoreceptors always synapse onto bipolar cells of each type, on center and off center Surround photoreceptors synapse on horizontal cells which mediate signals via lateral inhibitory connections Neural Circuits of Retinal Receptive Fields 37 Light stimulus on center: ¨↓ glu release from central photoreceptor ¨↓ inhibition of on-center bipolar cell à depolarization ¨↑ NT release à on-center ganglion cell excited ¨less glu available to excite off-centre bipolar cell à hyperpolarization ¨↓NT releaseà off-center ganglion cell inhibited light On center bipolar cells hyperpolarized by glutamate Neural Circuits of Retinal Receptive Fields 38 light light Light stimulus on surround: ¨↓ glu release from surround photoreceptor ¨↓ excitation of horizontal cells à ↓ inhibitory NT released ¨↓ inhibition of central photoreceptor à ↑ glu released ¨↑ glu hyperpolarizes on-center bipolar cell and depolarizes off-center bipolar cell ¨On-center ganglion cell inhibited, off-center ganglion cell excited Retinal receptive fields: outcome 39 ¨Surround arrangement and lateral inhibition allows ganglion cells to respond best to contrast borders in a visual scene ¤Ex. Reading dark letters against a white background ¤Respond only weakly to diffuse illumination ¤ B&L Figure 8-8 http://www.studentconsult.com/common/showimage.cfm?mediaISBN=9780323045827&FigFile=M9780323045827-0 08-f008.jpg&size=fullsize http://www.studentconsult.com/common/showimage.cfm?mediaISBN=9780323045827&FigFile=M9780323045827-0 08-f008.jpg&size=fullsize Light impinging on both center and surround of bipolar cell may result in cancellation of center and surround effects. Responses of amacrine cells depend on pattern of convergence from on-center and off-center bipolar cells (response involves increase or decrease in firing rate). Firing rate of ganglion cells is determined by input from bipolar and amacrine cells •dominant input from amacrine cells can produce uniform or mixed responses across receptive field •dominant input from bipolar cells produces center-surround responses Ganglion cell types and projections 40 Figure 12.14. Magno- and parvocellular streams. Lateral geniculate nucleus Visual pathway 41 E:\306\images\blks 6th ed\images\008009.jpg ¨Light from binocular zone strikes retina in both eyes ¨Monocular zone only strikes retina on same side as light The right visual field is projected to the ___________________ and ___________________ hemiretina The optic nerves segregate and carry information from ______________________ Each ___________________ crosses at the optic chiasm The optic tracts carry information from ______________________ to the brain ¨ Right temporal hemiretina Left temporal hemiretina Left/right nasal hemiretina Optic nerves Optic tracts B&L Figure 8-9 Left visual field Right visual field Fibers from the nasal hemiretina of each eye cross to the opposite side at the optic chiasm, whereas fibers from the temporal hemiretina do not cross. In the illustration, light from the right half of the binocular zone falls on the left temporal hemiretina and right nasal hemiretina. Axons from these hemiretinas thus contain a complete representation of the right hemifield of vision (see Figure 27-6). 42 43 Optical illusion 44 At the AUDITORY system is an array of miniature acoustical detectors packed into a space no larger than a pea. These detectors can faithfully transduce vibrations as small as the diameter of an atom, and they can respond a thousand times faster than visual photoreceptors Outer ear / middle ear Tympanic membrane Foramen rotundum m. tensor tympani Auditory ossicles maleus Incus stapes Temporal bone Tympanic cavity External auditory meatus Auditory tube Middle ear – transport acustic stimuli by air Scala vestibuli Membrana vestibularis membrána tectoria hair cells foramen rotundum 20 000Hz 1 500 Auditory tube – help for equilibrium of pressures – pressure inside the middle ear and barometric pressure) Inner ear – place for receptors Auditory tube The Audible Spectrum AnimalHz The Audible Spectrum Humans can detect sounds in a frequency range from about 20 Hz to 20 kHz. (Human infants can actually hear frequencies slightly higher than 20 kHz, but lose some high-frequency sensitivity as they mature; the upper limit in average adults is often closer to 15–17 kHz.) Not all mammalian species are sensitive to the same range of frequencies. Most small mammals are sensitive to very high frequencies, but not to low frequencies. For instance, some species of bats are sensitive to tones as high as 200 kHz, but their lower limit is around 20 kHz—the upper limit for young people with normal hearing. One reason for these differences is that small objects, including the auditory structures of these small mammals, are better resonators for high frequencies, whereas large objects are better for low frequencies (which also explains why the violin has a higher pitch than the cello). Middle ear: Impedance Matching Tympanic Membrane and the Ossicular System Conduction of Sound from the Tympanic Membrane to the Cochlea Figure 52–1 shows the tympanic membrane (commonly called the eardrum) and the ossicles, which conduct sound from the tympanic membrane through the middle ear to the cochlea (the inner ear). Attached to the tympanic membrane is the handle of the malleus. The malleus is bound to the incus by minute ligaments, so that whenever the malleus moves, the incus moves with it. The opposite end of the incus articulates with the stem of the stapes, and the faceplate of the stapes lies against the membranous labyrinth of the cochlea in the opening of the oval window. The tip end of the handle of the malleus is attached to the center of the tympanic membrane, and this point of attachment is constantly pulled by the tensor tympani muscle, which keeps the tympanic membrane tensed. This allows sound vibrations on any portion of the tympanic membrane to be transmitted to the ossicles, which would not be true if the membrane were lax. The ossicles of the middle ear are suspended by ligaments in such a way that the combined malleus and incus act as a single lever, having its fulcrum approximately at the border of the tympanic membrane. The articulation of the incus with the stapes causes the stapes to push forward on the oval window and on the cochlear fluid on the other side of window every time the tympanic membrane moves inward, and to pull backward on the fluid every time the malleus moves outward. “Impedance Matching” by the Ossicular System. The amplitude of movement of the stapes faceplate with each sound vibration is only three fourths as much as the amplitude of the handle of the malleus. Therefore, the ossicular lever system does not increase the movement distance of the stapes, as is commonly believed. Instead, the system actually reduces the distance but increases the force of movement about 1.3 times. In addition, the surface area of the tympanic membrane is about 55 square millimeters, whereas the surface area of the stapes averages 3.2 square millimeters. This 17-fold difference times the 1.3-fold ratio of the lever system causes about 22 times as much total force to be exerted on the fluid of the cochlea as is exerted by the sound waves against the tympanic membrane. Because fluid has far greater inertia than air does, it is easily understood that increased amounts of force are needed to cause vibration in the fluid. Therefore, the tympanic membrane and ossicular system provide impedance matching between the sound waves in air and the sound vibrations in the fluid of the cochlea. Indeed, the impedance matching is about 50 to 75 per cent of perfect for sound frequencies between 300 and 3000 cycles per second, which allows utilization of most of the energy in the incoming sound waves. In the absence of the ossicular system and tympanic membrane, sound waves can still travel directly through the air of the middle ear and enter the cochlea at the oval window. However, the sensitivity for hearing is then 15 to 20 decibels less than for ossicular transmission—equivalent to a decrease from a medium to a barely perceptible voice level. Transmission of Sound Waves in the Cochlea Transmission of Sound Waves in the Cochlea—“Traveling Wave” When the foot of the stapes moves inward against the oval window, the round window must bulge outward because the cochlea is bounded on all sides by bony walls.The initial effect of a sound wave entering at the oval window is to cause the basilar membrane at the base of the cochlea to bend in the direction of the round window. However, the elastic tension that is built up in the basilar fibers as they bend toward the round window initiates a fluid wave that “travels” along the basilar membrane toward the helicotrema, as shown in Figure 52–5. Figure 52–5A shows movement of a high- frequency wave down the basilar membrane; Figure 52–5B, a medium-frequency wave; and Figure 52–5C, a very low frequency wave. Movement of the wave along the basilar membrane is comparable to the movement of a pressure wave along the arterial walls, which is discussed in Chapter 15; it is also comparable to a wave that travels along the surface of a pond. The Organ of Corti Function of the Organ of Corti The organ of Corti, shown in Figures 52–2, 52–3, and 52–7, is the receptor organ that generates nerve impulses in response to vibration of the basilar membrane. Note that the organ of Corti lies on the surface of the basilar fibers and basilar membrane. The actual sensory receptors in the organ of Corti are two specialized types of nerve cells called hair cells—a single row of internal (or “inner”) hair cells, numbering about 3500 and measuring about 12 micrometers in diameter, and three or four rows of external (or “outer”) hair cells, numbering about 12,000 and having diameters of only about 8 micrometers. The bases and sides of the hair cells synapse with a network of cochlea nerve endings. Between 90 and 95 per cent of these endings terminate on the inner hair cells, which emphasizes their special importance for the detection of sound. The nerve fibers stimulated by the hair cells lead to the spiral ganglion of Corti, which lies in the modiolus (center) of the cochlea. The spiral ganglion neuronal cells send axons—a total of about 30,000—into the cochlear nerve and then into the central nervous system at the level of the upper medulla. The relation of the organ of Corti to the spiral ganglion and to the cochlear nerve is shown in Figure 52–2. Excitation of the Hair Cells ch13f6 Figure 13.6. Movement of the basilar membrane creates a shearing force that bends the stereocilia of the hair cells. The pivot point of the basilar membrane is offset from the pivot point of the tectorial membrane, so that when the basilar membrane is displaced, the tectorial membrane moves across the tops of the hair cells, bending the stereocilia. Excitation of the Hair Cells. Note in Figure 52–7 that minute hairs, or stereocilia, project upward from the hair cells and either touch or are embedded in the surface gel coating of the tectorial membrane, which lies above the stereocilia in the scala media.These hair cells are similar to the hair cells found in the macula and cristae ampullaris of the vestibular apparatus, which are discussed in Chapter 55. Bending of the hairs in one direction depolarizes the hair cells, and bending in the opposite direction hyperpolarizes them. This in turn excites the auditory nerve fibers synapsing with their bases. Figure 52–8 shows the mechanism by which vibration of the basilar membrane excites the hair endings. The outer ends of the hair cells are fixed tightly in a rigid structure composed of a flat plate, called the reticular lamina, supported by triangular rods of Corti, which are attached tightly to the basilar fibers. The basilar fibers, the rods of Corti, and the reticular lamina move as a rigid unit. Upward movement of the basilar fiber rocks the reticular lamina upward and inward toward the modiolus. Then, when the basilar membrane moves downward, the reticular lamina rocks downward and outward. The inward and outward motion causes the hairs on the hair cells to shear back and forth against the tectorial membrane.Thus, the hair cells are excited whenever the basilar membrane vibrates. Auditory Signals Are Transmitted Mainly by the Inner Hair Cells. Even though there are three to four times as many outer hair cells as inner hair cells, about 90 per cent of the auditory nerve fibers are stimulated by the inner cells rather than by the outer cells.Yet, despite this, if the outer cells are damaged while the inner cells remain fully functional, a large amount of hearing loss occurs. Therefore, it has been proposed that the outer hair cells in some way control the sensitivity of the inner hair cells at different sound pitches, a phenomenon called “tuning” of the receptor system. In support of this concept, a large number of retrograde nerve fibers pass from the brain stem to the vicinity of the outer hair cells. Stimulating these nerve fibers can actually cause shortening of the outer hair cells and possibly also change their degree of stiffness. These effects suggest a retrograde nervous mechanism for control of the ear’s sensitivity to different sound pitches, activated through the outer hair cells. Hair Cell Receptor Potentials and Excitation of Auditory Nerve Fibers. The stereocilia (the “hairs” protruding from the ends of the hair cells) are stiff structures because each has a rigid protein framework. Each hair cell has about 100 stereocilia on its apical border.These become progressively longer on the side of the hair cell away from the modiolus, and the tops of the shorter stereocilia are attached by thin filaments to the back sides of their adjacent longer stereocilia. Therefore, whenever the cilia are bent in the direction of the longer ones, the tips of the smaller stereocilia are tugged outward from the surface of the hair cell. This causes a mechanical transduction that opens 200 to 300 cation-conducting channels, allowing rapid movement of positively charged potassium ions from the surrounding scala media fluid into the stereocilia, which causes depolarization of the hair cell membrane. Thus, when the basilar fibers bend toward the scala vestibuli, the hair cells depolarize, and in the opposite direction they hyperpolarize, thereby generating an alternating hair cell receptor potential. This, in turn, stimulates the cochlear nerve endings that synapse with the bases of the hair cells. It is believed that a rapidly acting neurotransmitter is released by the hair cells at these synapses during depolarization. It is possible that the transmitter substance is glutamate, but this is not certain. Endocochlear Potential. To explain even more fully the electrical potentials generated by the hair cells, we need to explain another electrical phenomenon called the endocochlear potential: The scala media is filled with a fluid called endolymph, in contradistinction to the perilymph present in the scala vestibuli and scala tympani. The scala vestibuli and scala tympani communicate directly with the subarachnoid space around the brain, so that the perilymph is almost identical with cerebrospinal fluid. Conversely, the endolymph that fills the scala media is an entirely different fluid secreted by the stria vascularis, a highly vascular area on the outer wall of the scala media. Endolymph contains a high concentration of potassium and a low concentration of sodium, which is exactly opposite to the contents of perilymph. An electrical potential of about +80 millivolts exists all the time between endolymph and perilymph, with positivity inside the scala media and negativity outside. This is called the endocochlear potential, and it is generated by continual secretion of positive potassium ions into the scala media by the stria vascularis. The importance of the endocochlear potential is that the tops of the hair cells project through the reticular lamina and are bathed by the endolymph of the scala media, whereas perilymph bathes the lower bodies of the hair cells. Furthermore, the hair cells have a negative intracellular potential of –70 millivolts with respect to the perilymph but –150 millivolts with respect to the endolymph at their upper surfaces where the hairs project through the reticular lamina and into the endolymph. It is believed that this high electrical potential at the tips of the stereocilia sensitizes the cell an extra amount, thereby increasing its ability to respond to the slightest sound. Hair Cell Receptor Potentials ch13f8 Figure 13.8. Mechanoelectrical transduction mediated by hair cells. (A,B) When the hair bundle is deflected toward the tallest stereocilium, cation-selective channels open near the tips of the stereocilia, allowing K+ ions to flow into the hair cell down their electrochemical gradient (see text on next page for the explanation of this peculiar situation). The resulting depolarization of the hair cell opens voltage-gated Ca2+ channels in the cell soma, allowing calcium entry and release of neurotransmitter onto the nerve endings of the auditory nerve. (C) Receptor potentials generated by an individual hair cell in the cochlea in response to pure tones (indicated in Hz at the right of the tracings). Note that the hair cell potential faithfully follows the waveform of the stimulating sinusoids for low frequencies (<3kHz), but still responds with a DC offset to higher frequencies. (D) The stereocilia of the hair cells protrude into the endolymph, which is high in K+ and has an electrical potential of +80 mV relative to the perilymph. (A,B after Lewis and Hudspeth, 1983; C after Palmer and Russell, 1986.) Hair Cell Receptor Potentials and Excitation of Auditory Nerve Fibers. The stereocilia (the “hairs” protruding from the ends of the hair cells) are stiff structures because each has a rigid protein framework. Each hair cell has about 100 stereocilia on its apical border.These become progressively longer on the side of the hair cell away from the modiolus, and the tops of the shorter stereocilia are attached by thin filaments to the back sides of their adjacent longer stereocilia. Therefore, whenever the cilia are bent in the direction of the longer ones, the tips of the smaller stereocilia are tugged outward from the surface of the hair cell. This causes a mechanical transduction that opens 200 to 300 cation-conducting channels, allowing rapid movement of positively charged potassium ions from the surrounding scala media fluid into the stereocilia, which causes depolarization of the hair cell membrane. Thus, when the basilar fibers bend toward the scala vestibuli, the hair cells depolarize, and in the opposite direction they hyperpolarize, thereby generating an alternating hair cell receptor potential. This, in turn, stimulates the cochlear nerve endings that synapse with the bases of the hair cells. It is believed that a rapidly acting neurotransmitter is released by the hair cells at these synapses during depolarization. It is possible that the transmitter substance is glutamate, but this is not certain. Determination of Loudness Loudness is determined by the auditory system in at least three ways. First, as the sound becomes louder, the amplitude of vibration of the basilar membrane and hair cells also increases, so that the hair cells excite the nerve endings at more rapid rates. Chapter 52 The Sense of Hearing 657 Second, as the amplitude of vibration increases, it causes more and more of the hair cells on the fringes of the resonating portion of the basilar membrane to become stimulated, thus causing spatial summation of impulses—that is, transmission through many nerve fibers rather than through only a few. Third, the outer hair cells do not become stimulated significantly until vibration of the basilar membrane reaches high intensity, and stimulation of these cells presumably apprises the nervous system that the sound is loud. Detection of Changes in Loudness—The Power Law. As pointed out in Chapter 46, a person interprets changes in intensity of sensory stimuli approximately in proportion to an inverse power function of the actual intensity. In the case of sound, the interpreted sensation changes approximately in proportion to the cube root of the actual sound intensity. To express this another way, the ear can discriminate differences in sound intensity from the softest whisper to the loudest possible noise, representing an approximately 1 trillion times increase in sound energy or 1 million times increase in amplitude of movement of the basilar membrane.Yet the ear interprets this much difference in sound level as approximately a 10,000-fold change. Thus, the scale of intensity is greatly “compressed” by the sound perception mechanisms of the auditory system.This allows a person to interpret differences in sound intensities over an extremely wide range—a far wider range than would be possible were it not for compression of the intensity scale. Decibel Unit. Because of the extreme changes in sound intensities that the ear can detect and discriminate, sound intensities are usually expressed in terms of the logarithm of their actua l intensities.A 10-fold increase in sound energy is called 1 bel, and 0.1 bel is called 1 decibel. One decibel represents an actual increase in sound energy of 1.26 times. Another reason for using the decibel system to express changes in loudness is that, in the usual sound intensity range for communication, the ears can barely distinguish an approximately 1-decibel change in sound intensity. Threshold for Hearing Sound at Different Frequencies. Figure 52–9 shows the pressure thresholds at which sounds of different frequencies can barely be heard by the ear. This figure demonstrates that a 3000-cycle-per-second sound can be heard even when its intensity is as low as 70 decibels below 1 dyne/cm2 sound pressure level, which is one ten-millionth microwatt per square centimeter. Conversely, a 100-cycle-per-second sound can be detected only if its intensity is 10,000 times as great as this. Frequency Range of Hearing. The frequencies of sound that a young person can hear are between 20 and 20,000 cycles per second. However, referring again to Figure 52–9, we see that the sound range depends to a great extent on loudness. If the loudness is 60 decibels below 1 dyne/cm2 sound pressure level, the sound range is 500 to 5000 cycles per second; only with intense sounds can the complete range of 20 to 20,000 cycles be achieved. In old age, this frequency range is usually shortened to 50 to 8000 cycles per second or less, as discussed later in the chapter. Auditory Pathway ch13f11 Figure 13.11. Diagram of the major auditory pathways. Although many details are missing from this diagram, two important points are evident: (1) the auditory system entails several parallel pathways, and (2) information from each ear reaches both sides of the system, even at the level of the brainstem. How Information from the Cochlea Reaches Targets in the Brainstem A hallmark of the ascending auditory system is its parallel organization. This arrangement becomes evident as soon as the auditory nerve enters the brainstem, where it branches to innervate the three divisions of the cochlear nucleus. The auditory nerve (the major component of cranial nerve VIII) comprises the central processes of the bipolar spiral ganglion cells in the cochlea (see Figure 13.4); each of these cells sends a peripheral process to contact one or more hair cells and a central process to innervate the cochlear nucleus. Within the cochlear nucleus, each auditory nerve fiber branches, sending an ascending branch to the anteroventral cochlear nucleus and a descending branch to the posteroventral cochlear nucleus and the dorsal cochlear nucleus (Figure 13.11). The tonotopic organization of the cochlea is maintained in the three parts of the cochlear nucleus, each of which contains different populations of cells with quite different properties. In addition, the patterns of termination of the auditory nerve axons differ in density and type; thus, there are several opportunities at this level for transformation of the information from the hair cells Central Auditory Mechanisms Auditory Nervous Pathways Figure 52–10 shows the major auditory pathways. It shows that nerve fibers from the spiral ganglion of Corti enter the dorsal and ventral cochlear nuclei located in the upper part of the medulla. At this point, all the fibers synapse, and second-order neurons pass mainly to the opposite side of the brain stem to terminate in the superior olivary nucleus. A few second order fibers also pass to the superior olivary nucleus on the same side. From the superior olivary nucleus, the auditory pathway passes upward through the lateral lemniscus. Some of the fibers terminate in the nucleus of the lateral lemniscus, but many bypass this nucleus and travel on to the inferior colliculus, where all or almost all the auditory fibers synapse. From there, the pathway passes to the medial geniculate nucleus, where all the fibers do synapse. Finally, the pathway proceeds by way of the auditory radiation to the auditory cortex, located mainly in the superior gyrus of the temporal lobe. Several important points should be noted. First, signals from both ears are transmitted through the pathways of both sides of the brain, with a preponderance of transmission in the contralateral pathway. In at least three places in the brain stem, crossing over occurs between the two pathways: (1) in the trapezoid body, (2) in the commissure between the two nuclei of the lateral lemnisci, and (3) in the commissure connecting the two inferior colliculi. Second, many collateral fibers from the auditory tracts pass directly into the reticular activating system of the brain stem. This system projects diffusely upward in the brain stem and downward into the spinal cord and activates the entire nervous system in response to loud sounds. Other collaterals go to the vermis of the cerebellum, which is also activated instantaneously in the event of a sudden noise. Third, a high degree of spatial orientation is maintained in the fiber tracts from the cochlea all the way to the cortex. In fact, there are three spatial patterns for termination of the different sound frequencies in the cochlear nuclei, two patterns in the inferior colliculi, one precise pattern for discrete sound frequencies in the auditory cortex, and at least five other less precise patterns in the auditory cortex and auditory association areas. Firing Rates at Different Levels of the Auditory Pathways. Single nerve fibers entering the cochlear nuclei from the auditory nerve can fire at rates up to at least 1000 per second, the rate being determined mainly by the loudness of the sound. At sound frequencies up to 2000 to 4000 cycles per second, the auditory nerve impulses are often synchronized with the sound waves, but they do not necessarily occur with every wave. In the auditory tracts of the brain stem, the firing is usually no longer synchronized with the sound frequency, except at sound frequencies below 200 cycles per second. Above the level of the inferior colliculi, even this synchronization is mainly lost. These findings demonstrate that the sound signals are not transmitted unchanged directly from the ear to the higher levels of the brain; instead, information from the sound signals begins to be dissected from the impulse traffic at levels as low as the cochlear nuclei. We will have more to say about this later, especially in relation to perception of direction from which sound comes. Pro rovnovážný smysl sluchový i rovnovážný Inner ear vestibulum cochlea Semicircular canals Structure of hair cell Lateral movement stimulate receptor – receptor potencial Scala tympani scala media endolymfa perilymfa Scala media Membrana tectoria vnitřní vnější vláskové buňky The intensity of the sound is encoded as an amplitude receptor potential, in centripetal fibres As the frequency of AP; expression in decibels Pitch with frequency (number of waves/time) Odorant chemoreceptors Olfactory epithelium -Irritated by substances which: dissolves in nasal mucus, -area 5 cm2 -Phylogenetically the oldest sense - - -Henning's classification of odors: -Floral, fruity, bitumen, -Spicy, putrefactive, burnt - -Sensitive sense - (methyl mercaptan=garlic-400pg/1 l air) - receptors adapt quickly - - -Hypoosmia –anosmia - -hyperosmia Řasinky čichových receptorů-primární senzorické neurony Bulbus olfactorius Secundary olfactory neurons Tractus olfactorius Smell Layer of nasal mucosa Cilia olfactory sensory neurons The Olfactory Epithelium and Olfactory Receptor Neurons ch15f5 Figure 15.5. Structure and function of the olfactory epithelium. (A) Diagram of the olfactory epithelium showing the major cell types: olfactory receptor neurons and their cilia, sustentacular cells (that detoxify potentially dangerous chemicals), and basal cells. Bowman's glands produce mucus. Nerve bundles of unmyelinated neurons and blood vessels run in the basal part of the mucosa (called the lamina propria). Olfactory receptor neurons are generated continuously from basal cells. (B) Generation of receptor potentials in response to odors takes place in the cilia of receptor neurons. Thus, odorants evoke a large inward (depolarizing) current when applied to the cilia (left), but only a small current when applied to the cell body (right). (A after Anholt, 1987; B after Firestein et al., 1991.) The Olfactory Epithelium and Olfactory Receptor Neurons The transduction of olfactory information occurs in the olfactory epithelium, the sheet of neurons and supporting cells that lines approximately half of the nasal cavities. (The remaining surface is lined by respiratory epithelium, which lacks neurons and serves primarily as a protective surface.) The olfactory epithelium includes several distinct cell types (Figure 15.5A). The most important of these is the olfactory receptor neuron, a bipolar cell that gives rise to a small-diameter, unmyelinated axon at its basal surface that transmits olfactory information centrally. At its apical surface, the receptor neuron gives rise to a single process that expands into a knoblike protrusion from which several microvilli, called olfactory cilia, extend into a thick layer of mucus. The mucus that lines the nasal cavity and controls the ionic milieu of the olfactory cilia is produced by secretory specializations (called Bowman's glands) distributed throughout the epithelium. Two other cell classes, basal cells and sustentacular (supporting) cells, are also present in the olfactory epithelium. This entire apparatus—mucus layer and epithelium with neural and supporting cells—is called the nasal mucosa. The superficial location of the nasal mucosa allows the olfactory receptor neurons direct access to odorant molecules. Another consequence, however, is that these neurons are exceptionally exposed. Airborne pollutants, allergens, microorganisms, and other potentially harmful substances subject the olfactory receptor neurons to more or less continual damage. Several mechanisms help maintain the integrity of the olfactory epithelium in the face of this trauma. The respiratory epithelium, a non-neural epithelium found at the most external aspect of the nasal cavity, warms and moistens the inspired air. In addition, it secretes mucus, which traps and neutralizes potentially harmful particles. In both the respiratory and olfactory epithelium, immunoglobulins are secreted into the mucus, providing an initial defense against harmful antigens, and the sustentacular cells contain enzymes (cytochrome P450s and others) that catabolize organic chemicals and other potentially damaging molecules that enter the nasal cavity. The ultimate solution to this problem, however, is to replace olfactory receptor neurons in a normal cycle of degeneration and regeneration. In rodents, the entire population of olfactory neurons is renewed every 6 to 8 weeks. This feat is accomplished by maintaining among the basal cells a population of precursors (stem cells) that divide to give rise to new receptor neurons (see Figure 15.5A). This naturally occurring regeneration of olfactory receptor cells provides an opportunity to investigate how neural precursor cells can successfully produce new neurons and reconstitute function in the mature central nervous system, a topic of broad clinical interest. Recent evidence suggests that many of the signaling molecules that influence neuronal differentiation, axon outgrowth, and synapse formation in development elsewhere in the nervous system (see Chapters 22 and 23) perform similar functions for regenerating olfactory receptor neurons in the adult. Understanding how the new olfactory receptor neurons extend axons to the brain and reestablish appropriate functional connections is obviously relevant to stimulating the regeneration of functional connections elsewhere in the brain after injury or disease (see Chapter 25). 59 ch15f2 Olfactory System ch15f1 (C) Diagram of the basic pathways for processing olfactory information. (D) Central components of the olfactory system. (C) Diagram of the basic pathways for processing olfactory information. (D) Central components of the olfactory system. Central Projections of the Olfactory Bulb Glomeruli in the olfactory bulb are the sole target of olfactory receptor neurons, and thus the only relay—via the axons of mitral and tufted cells—for olfactory information from the periphery to the rest of the brain. The mitral cell axons form a bundle—the lateral olfactory tract—that projects to the accessory olfactory nuclei, the olfactory tubercle, the entorhinal cortex, and portions of the amygdala (see Figure 15.1A). The major target of the olfactory tract is the three-layered pyriform cortex in the ventromedial aspect of the temporal lobe near the optic chiasm. Although neurons in pyriform cortex respond to odors, there is no evidence of the predictable arrangement between receptor types and glomerular distribution found in the olfactory bulb. The further processing that occurs in this region is not well understood. The axons of pyramidal cells in the pyriform cortex project in turn to several thalamic and hypothalamic nuclei and to the hippocampus and amygdala. Some neurons from pyriform cortex also innervate a region in the orbitofrontal cortex comprising multimodal neurons that respond to olfactory and gustatory stimuli. Information about odors thus reaches a variety of forebrain regions, allowing olfactory cues to influence cognitive, visceral, emotional, and homeostatic behaviors 61 62 Physiological and Behavioral Responses to Odorants olfaction emotion Brain Scan Image Passion-Scent odorant molecules enter the nose and connect with odor receptors in the nasal epithelium. Electrochemical signals are generated in the olfactory bulb and are instantly transmitted to the limbic area of the brain. The diencephalon, in the limbic area, stimulates the production of dopamine and endorphins. Under the direction of these powerful brain chemicals, the body responds with increased physiological responses and heightened sensitivity to pleasurable sensations. Physiological and Behavioral Responses to Odorants In addition to olfactory perceptions, odorants can elicit a variety of physiological responses. Examples are the visceral motor responses to the aroma of appetizing food (salivation and increased gastric motility) or to a noxious smell (gagging and, in extreme cases, vomiting). Olfaction can also influence reproductive and endocrine functions. Women housed in single-sex dormitories, for instance, have menstrual cycles that tend to be synchronized. This phenomenon appears to be mediated by olfaction. Thus, volunteers exposed to gauze pads from the underarms of women at different stages of their menstrual cycles also tend to experience synchronized menses. Olfaction also influences maternal/child interactions. Infants recognize their mothers within hours after birth by smell, preferentially orienting toward their mothers' breasts and showing increased rates of suckling when fed by their mother compared to being fed by other lactating females (see also Chapter 24). By the same token, mothers can discriminate their own infant's odor when challenged with a range of odor stimuli from infants of similar age. In other animals, including many mammals, species-specific odorants called pheromones play important roles in behavior, by influencing social, reproductive, and parenting behaviors (Box A). In rats and mice, odorants thought to be pheromones are detected by G-protein-coupled receptors located at the base of the nasal cavity in distinct, encapsulated chemosensory structures called vomeronasal organs (VNO). Despite many attempts to identify pheromones in humans, there is little evidence for them. Indeed VNOs are found bilaterally in only 8% of adults and, there is no clear indication that these structures have any significant function in humans. Taste buds – taste chemoreceptors irritated by flavor substances dissolved in saliva Taste receptors in the cups on the mucous membrane of the tongue, epiglottis, palate and pharynx Ovoid shape, 50-60sterri, 40 own flavors Receptors=hair cells protruding into the oral cavity Afferent fibers adhere to the base of the taste bud (50 threads per 1 cup) Basic modalities: sweet – salt sour – bitter - umami (triggered by glutamate) Taste Gustatory afferent nerve Taste cell The Organization of the Taste System ch15f11 Figure 15.10. Organization of the human taste system. (A) Drawing on the left shows the relationship between receptors in the oral cavity and upper alimentary canal, and the nucleus of the solitary tract in the medulla. The coronal section on the right shows the VPM nucleus of the thalamus and its connection with gustatory regions of the cerebral cortex. (B) Diagram of the basic pathways for processing taste information. The Organization of the Taste System The taste system, acting in concert with the olfactory and trigeminal systems, indicates whether food should be ingested. Once in the mouth, the chemical constituents of food interact with receptors on taste cells located in epithelial specializations called taste buds in the tongue. The taste cells transduce these stimuli and provide additional information about the identity, concentration, and pleasant or unpleasant quality of the substance. This information also prepares the gastrointestinal system to receive food by causing salivation and swallowing (or gagging and regurgitation if the substance is noxious). Information about the temperature and texture of food is transduced and relayed from the mouth via somatic sensory receptors from the trigeminal and other sensory cranial nerves to the thalamus and somatic sensory cortices (see Chapters 9 and 10). Of course, food is not simply eaten for nutritional value; “taste” also depends on cultural and psychological factors. How else can one explain why so many people enjoy consuming hot peppers or bitter-tasting liquids such as beer? Like the olfactory system, the taste system includes both peripheral receptors and a number of central pathways (Figure 15.10). Taste cells (the peripheral receptors) are found in taste buds distributed on the dorsal surface of the tongue, soft palate, pharynx, and the upper part of the esophagus (Figure 15.10A; see also Figure 15.11). These cells make synapses with primary sensory axons that run in the chorda tympani and greater superior petrosal branches of the facial nerve (cranial nerve VII), the lingual branch of the glossopharyngeal nerve (cranial nerve IX), and the superior laryngeal branch of the vagus nerve (cranial nerve X) to innervate the taste buds in the tongue, palate, epiglottis, and esophagus, respectively. The central axons of these primary sensory neurons in the respective cranial nerve ganglia project to rostral and lateral regions of the nucleus of the solitary tract in the medulla (Figure 15.10B), which is also known as the gustatory nucleus of the solitary tract complex (recall that the posterior region of the solitary nucleus is the main target of afferent visceral sensory information related to the sympathetic and parasympathetic divisions of the visceral motor system; see Chapter 21). The distribution of these cranial nerves and their branches in the oral cavity is topographically represented along the rostral-caudal axis of the rostral portion of the gustatory nucleus; the terminations from the facial nerve are most rostral, the glossopharyngeal are intermediate, and those from the vagus nerve are more caudal. Integration of taste and visceral sensory information is presumably facilitated by this arrangement. The caudal part of the nucleus of the solitary tract also receives innervation from subdiaphragmatic branches of the vagus nerve, which control gastric motility. Interneurons connecting the rostral and caudal regions of the nucleus represent the first interaction between visceral and gustatory stimuli. This close relationship of gustatory and visceral information makes good sense, since an animal must quickly recognize if it is eating something that is likely to make it sick, and respond accordingly. Axons from the rostral (gustatory) part of the solitary nucleus project to the ventral posterior complex of the thalamus, where they terminate in the medial half of the ventral posterior medial nucleus. This nucleus projects in turn to several regions of the cortex, including the anterior insula in the temporal lobe and the operculum of the frontal lobe. There is also a secondary cortical taste area in the caudolateral orbitofrontal cortex, where neurons respond to combinations of visual, somatic sensory, olfactory, and gustatory stimuli. Interestingly, when a given food is consumed to the point of satiety, specific orbitofrontal neurons in the monkey diminish their activity to that tastant, suggesting that these neurons are involved in the motivation to eat (or not to eat) particular foods. Finally, reciprocal projections connect the nucleus of the solitary tract via the pons to the hypothalamus and amygdala (see Figure 15.10B). These projections presumably influence appetite, satiety, and other homeostatic responses associated with eating (recall that the hypothalamus is the major center governing homeostasis; see Chapter 21). Threshold for Taste The threshold for stimulation of the sour taste by hydrochloric acid averages 0.0009 N; for stimulation of the salty taste by sodium chloride, 0.01 M; for the sweet taste by sucrose, 0.01 M; and for the bitter taste by quinine, 0.000008 M. Note especially how much more sensitive is the bitter taste sense than all the others, which would be expected, because this sensation provides an important protective function against many dangerous toxins in food. Table 53–1 gives the relative taste indices (the reciprocals of the taste thresholds) of different substances. In this table, the intensities of four of the primary sensations of taste are referred, respectively, to the intensities of the taste of hydrochloric acid, quinine, sucrose, and sodium chloride, each of which is arbitrarily chosen to have a taste index of 1. Taste Blindness. Some people are taste blind for certain substances, especially for different types of thiourea compounds.A substance used frequently by psychologists for demonstrating taste blindness is phenylthiocarbamide, for which about 15 to 30 per cent of all people exhibit taste blindness; the exact percentage depends on the method of testing and the concentration of the substance. The Organization of the Peripheral Taste System Approximately 4000 taste buds in humans are distributed throughout the oral cavity and upper alimentary canal. Taste buds are about 50 mm wide at their base and approximately 80 mm long, each containing 30 to 100 taste cells (the sensory receptor cells), plus a few basal cells (Figure 15.11B-D). About 75% percent of all taste buds are found on the dorsal surface of the tongue in small elevations called papillae (see Figure 15.11A). There are three types of papillae: fungiform (which contain about 25% of the total number of taste buds), circumvallate (which contain 50% of the taste buds), and foliate (which contain 25%). Fungiform papillae are found only on the anterior two-thirds of the tongue; the highest density (about 30/cm2) is at the tip. They have a mushroom-like structure (hence their name) and typically have about 3 taste buds at their apical surface. There are 9 circumvallate papillae arranged in a chevron at the rear of the tongue. Each consists of a circular trench containing about 250 taste buds along the trench walls. Two foliate papillae are present on the posterolateral tongue, each having about 20 parallel ridges with about 600 taste buds in their walls. Thus, chemical stimuli on the tongue first stimulate receptors in the fungiform papillae and then in the foliate and circumvallate papillae. Tastants subsequently stimulate scattered taste buds in the pharynx, larynx, and upper esophagus. Taste cells in individual taste buds (see Figure 15.11C,D) synapse with primary afferent axons from branches of three cranial nerves: the facial (VII), glossopharyngeal (IX), and vagus (X) nerves (see Figure 15.10). The taste cells in fungiform papillae on the anterior tongue are innervated exclusively by the chorda tympani branch of the facial nerve; in circumvallate papillae, the taste cells are innervated exclusively by the lingual branch of the glossopharyngeal nerve; and in the palate they are innervated by the greater superior petrosal branch of the facial nerve. Taste buds of the epiglottis and esophagus are innervated by the superior laryngeal branch of the vagus nerve. The initiating events of chemosensory transduction occur in the taste cells, which have receptors on microvilli that emerge from the apical surface of the taste cell (see Figure 15.11D). The synapses that relay the receptor activity are made onto the afferent axons of the various cranial nerves at the basal surface. The apical surfaces of individual taste cells in taste buds are clustered in a small opening (about 1 mm) near the surface of the tongue called a taste pore. Like olfactory receptor neurons (and presumably for the same reasons), taste cells have a lifetime of only about 2 weeks and are normally regenerated from basal cells Taste Perception in Humans Most taste stimuli are nonvolatile, hydrophilic molecules soluble in saliva. Examples include salts such as NaCl needed for electrolyte balance; essential amino acids such as glutamate needed for protein synthesis; sugars such as glucose needed for energy; and acids such as citric acid that indicate the palatability of various foods (oranges, in the case of citrate). Bitter-tasting molecules include plant alkaloids, such as atropine, quinine, and strychnine, that may be poisonous. Placing bitter compounds in the mouth usually deters ingestion unless one “acquires a taste” for the substance, as for quinine in tonic water. The taste system encodes information about the quantity as well as the identity of stimuli. In general, the higher the stimulus concentration, the greater the perceived intensity of taste. Threshold concentrations for most ingested tastants are quite high, however. For example, the threshold concentration for citric acid is about 2 mM; for salt (NaCl), 10 mM; and for sucrose, 20 mM. Since the body requires substantial concentrations of salts and carbohydrates, taste cells may respond only to relatively high concentrations of these essential substances to promote an adequate intake. Clearly, it is advantageous for the taste system to detect potentially dangerous substances (e.g., bitter-tasting plant compounds) at much lower concentrations. Thus, the threshold concentration for quinine is 0.008 mM, and for strychnine 0.0001 mM. As in olfaction, gustatory sensitivity declines with age. Adults tend to add more salt and spices to food than children. The decreased sensitivity to salt can be problematic for older people with electrolyte and/or fluid balance problems. Unfortunately, a safe and effective substitute for NaCl has not yet been developed. There are at least two common misconceptions about taste perception. The first is that sweet is perceived at the tip of the tongue, salt along its posterolateral edges, sour along the mediolateral edges, and bitter on the back of the tongue. This arrangement was initially proposed in 1901 by Deiter Hanig, who measured taste thresholds for NaCl, sucrose, quinine, and hydrochloric acid (HCl). Hanig never said that other regions of the tongue were insensitive to these chemicals, but only indicated which regions were the most sensitive. People missing the anterior part of their tongue (or who have facial nerve lesions) can still taste sweet and salty stimuli. In fact, all of these tastes can be detected over the full surface the tongue (Figure 15.11A). However, different regions of the tongue do have different thresholds. Because the tip of the tongue is most responsive to sweet-tasting compounds, and because these compounds produce pleasurable sensations, information from this region activates feeding behaviors such as mouth movements, salivary secretion, insulin release, and swallowing. In contrast, responses to bitter compounds are indeed greatest on the back of the tongue. Activation of this region by bitter-tasting substances elicits protrusion of the tongue and other protective reactions that prevent ingestion. Sour-tasting compounds elicit grimaces, puckering responses, and massive salivary secretion to dilute the tastant. A second misconception about taste perception is that there are only four “primary” tastes: salt, sweet, sour, and bitter. If this were true, then all tastes could be represented as a combination of these “primaries.” Although these four tastes do indeed represent distinct perceptions, this classification is obviously limited. People experience a variety of additional taste sensations, including astringency (cranberries and tea), pungency (hot pepper and ginger), fat, starchy, and various metallic tastes (to name but a few). None of these, however, fits into these four categories. Moreover, some cultures consider other tastes to be “primary.” For example, the Japanese consider the taste of monosodium glutamate to be distinct from that of salt, and even give it a different name (“umami,” which means delicious). Finally, mixtures of various chemicals may elicit entirely new taste sensations. While it is possible to estimate the number of perceived odors (approximately 10,000), these uncertainties have made it difficult to estimate the number of tastes. In neither taste nor olfaction is there a clear relationship between “primary” perceptual classes and the cellular and molecular machinery of sensory transduction. Central Processing of Taste Signals ch15f10 Central Processing of Taste Signals If the labeled line theory is correct, the physiological properties of distinct taste receptor cells in the periphery should be faithfully projected to the central relay stations of the taste system. There is, in fact, some evidence for “best” taste responses in the nucleus of the solitary tract, thalamus, and cortex. For instance, the drug amiloride has been shown to inhibit the responses to NaCl only from NaCl-best neurons in the central nervous system, as it does for the NaCl-best primary afferents. It is important to note, however, that “best” types are determined by evaluating a limited number of taste stimuli at a limited number of concentrations. In addition, gustatory information contains information about quality, intensity, and hedonic value, all of which are unlikely to be encoded in a single type of neuron. In short, given present evidence, it is difficult to prove the validity of the labeled line theory. If the ensemble or across neuron model is correct, patterns of activation across subsets of neurons should be apparent, and these patterns should be associated with stimulation by particular tastants (see Figure 15.14B). In the presence of amiloride, the patterns for NaCl and KCl are very similar, and rats cannot distinguish between them. The pattern of activity elicited by a single stimulus in a set of taste-responsive neurons does indeed remain relatively stable at a particular stimulus concentration, although increasing the concentration recruits new neurons, thus changing the pattern and the taste. In keeping with this ensemble model, mixtures of stimuli tend to have unique patterns of activity, and unique tastes are experienced that cannot easily be described as a combination of the alleged four or five “primary” tastes. Markedly changing the pattern changes the taste and, the closer the patterns, the closer the tastes. The tuning curves for neurons in the solitary nucleus, thalamus, and cortex become ever more broadly tuned to stimuli that are nonetheless perceptually distinct, suggesting that ensembles of neurons extract specific information about chemicals placed in the oral cavity. Moreover, many of the neurons in the gustatory cortices are multimodal: They respond to thermal, mechanical, olfactory, and visual stimuli pertaining to food, as well as to taste stimuli. In summary, neural coding for taste, as for olfaction, involves information obtained from ensembles of neurons from many interacting neural subsystems and cannot, based on present evidence, be reduced to a single conceptual scheme. Taste pathways From the front 2/3 of the tongue –chorda tympani – nervus trigeminal From the back – glossopharyngeus nerve Receptors are also adaptable, Low resolution between two substances Constantly renewed Hypogeuzia (decrease in taste activity) ageuzia - hypergeuzia Tractus solitarius n.facialis Chorda tympani n.trigeminus n.glossophar. 68 69