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Welcome to Clinical anatomy of the head, neck and neuronal pathways
Lecture #7
Department of Anatomy
MUNI, MED
Alemeh Zamani, Ph.D.
Spring 2024
Future Lectures
Somatosensory and viscerosensory; pain pathways and connections of stress analgesia
Pathways of the somatomotor system, connections of the cerebellum and basal ganglia; spinal
reflex motoric; eye movements
Arrangement and function of the autonomic nervous system
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Today’s lecture will cover:
1- Nervous System Barriers
2- Plasticity and Regeneration of Nervous System
3- Visual and Auditory Pathways
4- Vestibular, Olfactory, and Gustatory Pathways
Today’s lecture will cover:
1- Nervous System Barriers
2- Plasticity and Regeneration of Nervous System
3- Visual and Auditory Pathways
4- Vestibular, Olfactory, and Gustatory Pathways
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Nervous System Barriers
o Blood-Brain Barrier
o Blood-Spinal Cord Barrier
o Blood-Cerebrospinal Fluid Barrier
o Blood-Nerve Barrier
o Blood-DRG Barrier
Blood-Brain Barrier Blood-CSF Barrier
Blood-spinal cord BarrierBlood-retinal barrier
Blood-arachnoid Barrier
Blood-Brain Barrier -Tatiana Barichello
Blood-Brain Barrier (BBB)
Blood-Brain Barrier -Tatiana Barichello
Neurovascular unit
➢ BBB is formed by a tight monolayer of brain endothelial cells.
➢ Function of BBB is maintaining brain homeostasis by regulating
transport to the brain.
➢ The plasticity of BBB is regulated within a dynamic system called
Neurovascular unit.
➢ BBB represents a significant roadblock in delivering drugs to brain.
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Blood-Brain Barrier
❖ Junctional proteins and transporters:
Junctional Proteins Transporter Proteins
Neuroscience Online, the Open-Access Neuroscience Electronic Textbook
small inorganic molecules (O2, CO2, NO, and H2O)
ions, peptides, amino acids, proteins, carbohydrates,
hormones, vitamins, etc.
Non-barrier regions (hormonal control)
o Pituitary gland
o Median eminence
o Area postrema
o Preoptic recess
o Paraphysis
o Pineal gland
o Endothelium of choroid plexus
Ufnal, Neuropeptides 2014
Circumventricular organs (CVOs)
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Blood-Brain Barrier Dysfunction
Dysregulated BBB transport in Alzheimer’s disease
BBB dysfunction is associated with neurological disorders:
Neurodegenerative diseases, Cerebrovascular diseases, Brain infections, Inflammatory diseases, Brain tumors,
Neurotrauma, Mental or psychological stress
Disruption of BBB can lead to:
o Changes in permeability
o Modulation of immune cell transport
o Trafficking of pathogens into the brain
Storck, Neuroforum 2017
Blood-Spinal Cord Barrier (BSCB)
Bartanusz, Annals of Neurology, 2011
Composed of continuous type of microvessels
More permeable for cytokines and tracers compared to BBB:
o Lower level of occludin and ZO-1
o Less number of pericytes
o Spinal cord injury
o Amyotrophic lateral sclerosis
o Radiation‐induced myelopathy
Pathological conditions:
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Blood-CSF Barrier
Lun, Nature Reviews Neuroscience 2015
Epithelial cells of choroid plexus:
o Secrete cerebrospinal fluid (CSF)
o Form blood-CSF barrier
Role of blood-CSF barrier
o To restrict the passage of substances from blood into CSF
Blood-CSF Barrier Dysfunction
Pathogen invasion through B-CSF barrier
Solár, Fluids Barriers CNS, 2020
Blood-CSF barrier permeability alteration:
o Infectious disease
o Stroke
o Trauma
o Neurodegenerative disease
o Autoimmune disorders
o Tumors of choroid plexus
o Schizophrenia and chronic stress
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Reinhold, Experimental neurology 2020
Blood-Nerve Barrier (BNB)
Endoneurial fluid = CSF
Blood-nerve exchange is maintained by endothelial cells of endoneurial vessels.
❖ Perineurial cells interaction with Schwann cells critical for
nerve development and regeneration
Wallerian Degeneration
Injury of nerves and axons
o Proliferation of Schwann cells
o Invasion of circulating macrophages
o Alteration of the blood-nerve barrier
o Changes in the endoneurial extracellular matrix
o Elevation of cytokine production
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Blood-Dorsal Root Ganglion (DRG) Barrier
Reinhold, Experimental neurology 2020
Present in DRG
o Somata of sensory nerves
o Nociceptive neurons
More permeable than the BNB
Peripheral nerve injury induces cellular and molecular changes in the DRG that contribute to induction and
maintenance of neuropathic pain.
Today’s lecture will cover:
1- Nervous System Barriers
2- Plasticity and Regeneration of Nervous System
3- Visual and Auditory Pathways
4- Vestibular, Olfactory, and Gustatory Pathways
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Plasticity and Regeneration of Nervous System
Brain never stops changing …❖ Neuronal plasticity is defined as the ability of NS to modify the
activity and organization of neuronal circuitry according to
internal or external stimuli:
o Alterations in the level of the neurotransmitters
o Change in the protein content at synapses
Short-term and long-term potentiation and depression, milliseconds to hours or even longer
o Adaptational plasticity
Continuous adjustment in response to environmental challenges
o Reparation plasticity
Positive or negative changes during functional or structural recovery of damaged neuronal circuits
The correction of developmentally miswired neuronal connections or rehabilitation after stroke or traumatic brain
injury depend crucially on the adult brain’s capacity for plasticity.
Reparation Plasticity
Reaction to injury differs in neurons of CNS and PNS
CNS
o Damage to neurons, glial, and endothelial cells
o Breakdown of the blood-brain barrier
o Activation of glial cells and a robust inflammatory response
Adult mammalian CNS has a limited regenerative capacity
Silver, Cold Spring Harb Prospect Biol 2015
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CNS Pathology after a Traumatic Injury
Mietto, Mediators of Inflammation 2015
Inhibitory molecules for CNS regeneration:
o Chondroitin Sulfate Proteoglycans (from astroglial scar)
o Myelin-Associated Inhibitors (from oligodendrocytes)
o Inhibitory Signaling Pathways (Ibuprofen inhibits RhoA )
Pro-regenerative molecules
NGF, TGF-𝛽, PDGF, EGF, BDNF, and oncomodulin
Glial environment of the adult CNS presents a major hurdle for successful axon regeneration
Peripheral Nerve Pathology after a Traumatic Injury
Regeneration of PNS neurons depends on
o type of injury
o age of the organism
o localization and function of neurons
Schwann cells: overexpress a broad panel of
inflammatory mediators
Macrophages: phagocytosis of cellular debris
Navarro, Progress in Neurobiology 2007
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Cellular and molecular mechanisms during PNS regeneration
Regeneration-Associated Genes
o c-Jun
o activating transcription factor-3 (ATF-3)
o SRY-box containing gene 11 (Sox11)
o small proline-repeat protein 1A (SPRR1A)
o growth-associated protein-43 (GAP-43)
o CAP-23
Huebner, Results Probl Cell Differ 2009
❖ Neuroma = Result of disorganized growth of cone
branches in an unsuccessful search of a receptor
or endoneurial tube is not reached, = painful lump
Grinsell, BioMed Research Internationall 2014.
Today’s lecture will cover:
1- Nervous System Barriers
2- Plasticity and Regeneration of Nervous System
3- Visual and Auditory Pathways
4- Vestibular, Olfactory, and Gustatory Pathways
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Visual Pathways
Perception of motion, depth, form and color
Boron, Medical Physiology, 2003
Joukal, Anatomy of the Human Visual Pathway
Neuronal elements of visual pathway
v
v
Photopic vision
perception of shape and color
Photopsin
Cone (5 -7 million)
Scotopic vision
dim light
Rhodopsin
Rod (100-130 million)
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P cells (80%)
o ganglion cells that monitor cones
o color-specific
o terminate on P-neurons of the lateral geniculate body
M cells (10%)
o ganglion cells that monitor rods
o provide information about a general form of an object
o terminate on M-neurons of the lateral geniculate body
non-P non-M cells (10%)
o projection to subcortical nuclei, koniocellular cells of LGN
Neuronal elements of visual pathway
Joukal, Anatomy of the Human Visual Pathway
L L RR
Ipsilateral fibers
Contralateralfibers
Pimary Visual Pathway
Joukal, Anatomy of the Human Visual Pathway
Monocular blindness
❖ 10% of axons at LGN
terminate in the tectum of the
mesencephalon.These fibers
are important for optic
reflexes, such as pupillary
reflex or vestibulo-ocular
reflex.
Optic nerve
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❖ Ipsilateral input enters
layers 2,3 and 5 of LGN
❖ Contralateral input enters
layers 1, 4 and 6 of LGN
Fibers crossing temporal lobe:
inferior lateral fibers or meyer's
loop
Fibers crossing parietal lobe:
superior retinal fiber
Joukal, Anatomy of the Human Visual Pathway
Primary Visual Cortex
The Visual Cortex
Extrastriate Visual Cortex
Joukal, Anatomy of the Human Visual Pathway
The ventral stream
Information about object identification including shape, contrast, and
color, “what” pathway
The dorsal stream
Information about spatial features and movement, “where” pathway
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Bitemporal hemianopsia Homonymous hemianopsia Scotoma
Lesions of the visual pathway
Joukal, Anatomy of the Human Visual Pathway
Optic chiasm Optic tract
Striate area
Auditory Pathways
The perception of sound; the most important means of communication
organ of Corticross section of the cochlea
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Diagram of the major auditory pathways
2nd order neuron
o Dorsal cochlear nucleus
→ nucleus of lateral lemniscus
o Ventral cochlear nucleus:
➢ VPCN → ?
➢ AVCN → superior olivary nucleus (trapezoid body)
3rd order neuron
o nucleus of inferior colliculus
4th order neuron
o medial geniculate nucleus
(brachium of inferior colliculus)
1st order neuron
o Spiral ganglion cells
Auditory pathway:
o Sensory hair cells
o Cochlear branch of vestibulocochlear nerve (C.N. VIII, Auditory Nerve):
Spiral ganglion cells →
o Brainstem: cochlear nucleus:
DCN → nucleus of lateral lemniscus →
VPCN → nucleus of inferior colliculus
AVCN → superior olivary nucleus →
o Midbrain: nucleus of inferior colliculus →
o Thalamus: medial geniculate nucleus →
o Auditory cortex
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Temporal superior gyrus (Heschl gyrus)
In Wernicke's area speech is comprehended.
Auditory cortex
Sound localization
Two functionally significant features of ascending pathway:
o tonotopical organization
o bilateral projection
Ascending and Descending pathways
Descending pathway functions (superior olivary complex):
o feedback system processing ascending information
o enhance signals
o supress noise
o focus on a particular speaker
o inhibit other voices
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Bilateral lesions in cortical deafness
o Hearing impairments
o Impairments of speech comprehension
o Speech repetition impairment
o Impairment in recognition of familiar sounds and music
Pathology
Today’s lecture will cover:
1- Nervous System Barriers
2- Plasticity and Regeneration of Nervous System
3- Visual and Auditory Pathways
4- Vestibular, Olfactory, and Gustatory Pathways
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Vestibular Pathways
Vestibular information is used for:
o Control eye movements
o Maintain statice and dynamic equilibrium
o Conscious awareness of ourselves in “space”
3 afferent sources:
o Eyes
o General proprioceptive receptors throughout the body
o Vestibular receptors in the inner ear
Vestibular Apparatus
o Receptors of static apparatus (linear acceleration- gravity)
o macula utriculi – orientation in horizontal position
o macula sacculi – orientation in vertical position
o Receptors of dynamic apparatus (angular acceleration- rotation of the head)
o cristae ampullares of semicircular ducts
Static organ
Kinetic organ
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Vestibular pathways
Connections with the spinal cord
To motoneurons that innervate axial and proximal limb muscles
o Lateral vestibulospinal tract
o from lateral vestibular nucleus
o uncrossed
o terminating at all levels of the spinal cord
o excitatory influences for extensors
Support body against gravity
o Medial vestibulospinal tract
o from medial vestibular nucleus
o uncrossed
o terminates mainly at cervical levels
o coordination of head position and eye movements
Marc, Fundamental Neuroscience 2013
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Connections with the cerebellum
o Vestibular nucleus inferior cerebellar peduncles
vestibulocerebellum (Fastigial nucleus)
o Fastigial nucleus inferior cerebellar peduncles
vestibular nucleus (vestibulospinal tract )
Maintenance of balance
Connections with the brain stem
Medial vestibular nucleus CN VI
Coordination of eye movements in response to head movements
CN III
CN IV
Eye’s muscle
horizontal
ventricle
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Connections with the cortex
Conscious perception of movement and gravity
Thalamus: Ventral posteromedial nucleus
o Area 2v at the tip of the intraparietal sulcus
o Parieto-insular vestibular cortex (PIVC) at the posterior end of the insula
o Area 7 in the inferior parietal lobule
No primary vestibular cortex
Brant, Vestibular cortex: its locations, functions, and disorders
Natural stimulation of the vestibular system during head motion and
locomotion is always multisensory (visual, vestibular, somatosensory)
Distributed among several multisensory areas in the parietal and temporal cortices
Vestibular Impairment
Cortical representation of vestibular information is important for cognition, emotion and the sense of self.
Disturbance in the body's balance system
Symptoms:
Dizziness, vertigo, nausea, vomiting, intolerance to head
motion, nystagmus, unsteady gait, and postural instability.
Acoustic Neuroma
Age-related dizziness and imbalance
Bilateral Vestibular Hypofunction
Cognitive and emotional disorders
Symptoms:
feeling “spaced out”, “body feeling strange” and “not feeling in control of self”
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Olfactory Pathways
Humans are capable of discriminating a great variety of odors and flavors.
1st order neuron: bipolar olfactory neurons
Olfactory Pathways
Olfactory neurons are distinctive among neurons in that they are
short-lived, with an average life span of only 30-60 days, and are
continuously replaced from the basal stem cell population.
Kandel, Samell and tatste; the chemical senses
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2nd order neuron: mitral cells lateral olfactory tract
Olfactory Pathways
Olfactory information is processed in several regions of the cerebral cortex.
3rd order neuron: olfactory tubercle
4th order neuron: dorsomedial nucleus of thalamus
Olfactory Pathways
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Olfactory Pathways
Olfactory nerve is divided to:
o Lateral olfactory stria
o Medial olfactory stria
Pathology
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Gustatory Pathways
Sense of taste
The distribution and types of human lingual papillae
Taste buds
o receptor cells (replaced about every 9-10 days by differentiating basal cells)
o supportive columnar cells
o basal cells
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1st order neuron
o CN VII (facial nerve) – geniculate ganglion (chorda tympani)
o CN IX (glossopharyngeal) – inferior ganglion of CN IX
o CN X (vagus)– nodose ganglion (inferior ganglion of CN X)
2/3 1/3
Gustatory pathway
2nd order neuron - rostral part of the solitary tract nucleus
3rd order neuron – ventral posteromedial nucleus of thalamus
Gustatory pathway
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Primary gustatory cortex
o a. 43 in the postcentral gyrus
o insula
Gustatory pathway
Oral sources of altered taste function are common and can be evaluated by a dentist.
Gustatory impairment
Gustatory dysfunctions:
o quantitative disorders
a. Ageusia
b. Hypogeusia
c. hypergeusia
o qualitative disorders
a. Dysgeusia
b. phantogeusia
Maheswaran, J Pharm Bioallied Sci 2014
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Reading list
Thank you very much for your attention