Introduction to neurophysiology Cellular base of nervous system Synapse Introduction-cellular base-synapse2 Contact Kamil Ďuriš Department of Pathological Physiology (A18) kduris@med.muni.cz Introduction-cellular base-synapse3 Why and how to STUDY neuroscience Philosophy : Mind behind Mind Psychology : MindNeuroscience: Brain PS Deb http://www.slideshare.net/drpsdeb/presentations FACTS THEORIES Introduction-cellular base-synapse4 What is nervous system good for? Introduction-cellular base-synapse5 Introduction-cellular base-synapse6 The role of nervous system Multicellular organism • Functional specialization of particular cells – higher effectivity • Inner environment – homeostasis • Lower level of stress • Longer life time Unicellular organism • One cell has to do everythinglower effectivity • Total dependence on environment • High level of stress • Short life time The role of nervous system • Essentials for survival of multicellular organism ➢ Maintaining homeostasis – The composition of inner environment – The integrity of organ/ bodily barriers ➢ Coordination of bodily functions – To receive signals from outer and inner environment – To process this information – To respond in a coordinate manner to these stimuli Introduction-cellular base-synapse7 Input Integration Output REGULATION • Regulation – Nervous – Humoral The role of nervous system Introduction-cellular base-synapse8 • Regulation – Nervous – Humoral http://biology.about.com/od/anatomy/p/Hypothalamus.htm The role of nervous system Central nervous system controls both types of regulations Introduction-cellular base-synapse9 The role of nervous system Humoral regulations • Hormone • Non-specific channel of conduction (blood stream) • Target site defined by specific receptor • Low energetical demands • Slow • Long duration Nervous regylations • Neurtransmitters • Specific channel of conduction • Target site defined by infrastructure • High energetical demands • Fast • Short duration Introduction-cellular base-synapse10 The role of nervous system Humoral regulations • Hormone • Non-specific channel of conduction (blood stream) • Target site defined by specific receptor • Low energetical demands • Slow • Long duration Nervous regylations • Neurtransmitters • Specific channel of conduction • Target site defined by infrastructure • High energetical demands • Fast • Short duration Introduction-cellular base-synapse11 The role of nervous system Introduction-cellular base-synapse12 Input Integration Output REGULATION The role of nervous system Introduction-cellular base-synapse13 Input Integration Output REGULATION Potential input Potential output ANTICIPATION The role of nervous system Introduction-cellular base-synapse14 Input Integration Output REGULATION Potential input Potential output ANTICIPATION Sensor Effector Cortex Cortex Evolutionary approach • Evolutionary old structures have not been replaced by new ones during evolution, but the old has been kept and the new added • Evolutionary younger structures were associated with new functions or with the improvement in existing functions • It is important to ask what is any particular function good for and how it has been improved in course of evolution Introduction-cellular base-synapse15 Evolutionary approach • Evolutionary old structures have not been replaced by new ones during evolution, but the old has been kept and the new added • Evolutionary younger structures were associated with new functions or with the improvement in existing functions • It is important to ask what is any particular function good for and how it has been improved in course of evolution Introduction-cellular base-synapse16 Evolutionary approach • Evolutionary old structures have not been replaced by new ones during evolution, but the old has been kept and the new added • Evolutionary younger structures were associated with new functions or with the improvement in existing functions • It is important to ask what is any particular function good for and how it has been improved in course of evolution Introduction-cellular base-synapse17 Evolutionary approach Evolution is not revolution Introduction-cellular base-synapse18 Evolution of the nervous system Gerald Schneider. 9.14 Brain Structure and Its Origins, Spring 2014. (Massachusetts Institute of Technology: MIT OpenCourseWare), http://ocw.mit.edu (Accessed). License:Creative Commons BY-NC-SA Introduction-cellular base-synapse19 Four basic types of tissue ✓ Epithelial ✓ Connective ✓ Muscular ✓ Nervous Input Integration Output Evolution of the nervous system Gerald Schneider. 9.14 Brain Structure and Its Origins, Spring 2014. (Massachusetts Institute of Technology: MIT OpenCourseWare), http://ocw.mit.edu (Accessed). License:Creative Commons BY-NC-SA Introduction-cellular base-synapse20 Input Integration Output Evolution of the nervous system Introduction-cellular base-synapse21 Gerald Schneider. 9.14 Brain Structure and Its Origins, Spring 2014. (Massachusetts Institute of Technology: MIT OpenCourseWare), http://ocw.mit.edu (Accessed). License:Creative Commons BY-NC-SA Input Integration Output Compartmentalization • Cellular specialization leads to compartmentalization on several levels – Tissue level – Organ level – Organ system level • There are barriers in between compartments • Properties/content may vary among different compartments Introduction-cellular base-synapse22 Compartmentalization • Cellular specialization leads to compartmentalization on several levels – Tissue level – Organ level – Organ system level • There are barriers in between compartments • Properties/content may vary among different compartments Introduction-cellular base-synapse23 v v Intracranial compartment Introduction-cellular base-synapse24 ✓ „Very specific region“ ✓ Brain ✓ Cerebrospinal fluid ✓ Blood (intravasculary) ✓ Barriers • Meningeal • Hematoliquor • Hematoencephalic http://edutoolanatomy.wikispaces.com http://www.corpshumain.ca/en/Cerveau3_en.php Hematoencephalic barrier • Highly organised structure – Endothelial cells (low permeability thanks to zonlua occludens) – Basal membrane – Astrocytes – Pericytes Introduction-cellular base-synapse25 https://upload.wikimedia.org/wikipedia/commons/1/12/Blood_vessels_brain_english.jpg Circumventricular organs • Rich vascularisation • Modified hematoencephalic barrier • Sensors • Secretion Introduction-cellular base-synapse26 http://www.neuros.org/index.php?option=com_photos&view=photos&oid=hafizbilal Cerebrospinal fluid • Content ✓ High levels of Mg+ and Na+ ✓ Low levels of K+ and Ca2+ ✓ Almost no cells (max 5/ml) • Function ✓ Protection ✓ Microenvironment of neurons and glia – Metabolic function – Immunologic function – Transport function and so on Introduction-cellular base-synapse27 http://www.control.tfe.umu.se PCh AG Cerebrospinal fluid • Clear fluidproduced by active secretion • Liquor space ➢ lined by ependymal cells ➢ 150-250 ml • Production ✓ Plexus choroideus (PCh) -70% ✓ Cell metabolism ✓ Cappilary filtration ➢ 450-750 ml/day • Resorbtion ✓ Archnoid granulations (AG) Introduction-cellular base-synapse28 http://www.control.tfe.umu.se PCh AG Intracranial compartment Introduction-cellular base-synapse29 • Brain • Cerebrospinal fluid • Blood (intravasculary) • Intracranial pressure (ICP) • Critical determinant of cerebral perfusion • Cerebral perfusion pressure (CPP) pressure gradient driving blood flow intracranialy http://edutoolanatomy.wikispaces.com !!! CPP = MAP – ICP !!! Cerebral perfusion pressure Mean arterial pressure Intracranial pressure Cellular base of nervous system Synapse Introduction-cellular base-synapse30 Cellular base of nervous system • Neuronal cells – Reception, integration and propagation of information – Unique, irreplaceable • Neuroglial cells – Support for neuronal cells – Easily replacable • The total amount of neuronal cells - 100 billions (1011) • Neruon/glia ratio – 1/10 - 50 (Principles of Neural Science, 4th ed., 2012) – 1/2 – 10 (Principles of Neural Science, 5th ed., 2012) – 1/1 (Nolte´s Human Brain, 7th ed., 2015) Introduction-cellular base-synapse31 Neuroglial cells Introduction-cellular base-synapse32 Central nervous system Peripheral nervous system • Astrocytes – Hematoencephalic b. – Homeostasis maintaining – Metabolism of neurotransmitters – Important during brain development • Oligodendrocytes – Myelin sheat • Microglia – Immune funtion • Ependymal cells – Choroid plexus – (hemato-liquor barrier) – Ventricular lining (liquro-encephalic barrier) • Satelite cells – Support functions in PNS • Schwan cells – Myelin sheat Neuron Introduction-cellular base-synapse33 http://www.slideshare.net/drpsdeb/presentations The inside of the cell ✓ … ✓ Synthesis ✓ Transport ✓ … ✓ Signal reception ✓ Signal integration ✓ AP generatin ✓ AP propagation ✓ Signal transmission The membrane Background Activity Introduction-cellular base-synapse34 https://upload.wikimedia.org/wikipedia/commons/e/ed/Neuron_Cell_Body.png Background Activity Introduction-cellular base-synapse35 https://upload.wikimedia.org/wikipedia/commons/e/ed/Neuron_Cell_Body.png Background Activity Introduction-cellular base-synapse36 http://www.oapublishinglondon.com/images/article/pdf/1397255957.pdf Membrane potential • Due to differences in the concentrations of ions on opposite sides of a cellular membrane Introduction-cellular base-synapse37 http://www.slideshare.net/drpsdeb/presentations Resting membrane potential of a neuron • Highly instable state of membrane • Why? – Speed! • High energetical demands ✓ Oxygen - 20% of total body consumption ✓ Glucose – 25% of total body consumption Introduction-cellular base-synapse38 http://assassinscreed.ubi.com Action potential • Quick voltage change on the membrane • Spreads along the axon • All or nothing principle Introduction-cellular base-synapse39 http://www.slideshare.net/drpsdeb/presentations Action potential spreading • Local currents • Anterograde Introduction-cellular base-synapse40 http://www.slideshare.net/drpsdeb/presentations Saltatory conduction • Myelin sheat • Nodes of ranvier • Economy • Speed of conduction • Speed of conduction also dependent of nerve fibre diameter – the electrical resistance is inversly proportional to area of cross- section Introduction-cellular base-synapse41 http://www.slideshare.net/drpsdeb/presentations • In humans mostly myelinated • All fibers are myelinated in CNS • Non-myelinated are evolutionary old ones Introduction-cellular base-synapse42 Classification of nerve fibers http://neuroscience.uth.tmc.edu/s2/chapter04.html Neuronal classification 43 http://www.slideshare.net/CsillaEgri/presentations Introduction-cellular base-synapse Neuronal classification Introduction-cellular base-synapse44 http://www.slideshare.net/CsillaEgri/presentations Neuronal classification Introduction-cellular base-synapse45 http://www.slideshare.net/CsillaEgri/presentations Synapse Introduction-cellular base-synapse46 • Communication between neurons • Electrical • Chemical Electrical synapse Introduction-cellular base-synapse47 • Evolutionary old • Less frequent than ch. • Ubiquitous • Gap junctions • Bidirectional tranmission • Fast • Strength of signal may decrease http://www.slideshare.net/CsillaEgri/presentations Electrical synapse Introduction-cellular base-synapse48 • Evolutionary old • Less frequent than ch. • Ubiquitous • Gap junctions • Bidirectional tranmission • Fast • Strength of signal may decrease http://www.slideshare.net/CsillaEgri/presentations Chemical synapse Introduction-cellular base-synapse49 • Evolutionary young • Majority type of s. • Unidirectional • Synaptic cleft • Neurotransmitter • Constant signal strength http://www.slideshare.net/CsillaEgri/presentations Chemical synapse Introduction-cellular base-synapse50 • Evolutionary young • Majority type of s. • Unidirectional • Synaptic cleft • Neurotransmitter • Constant signal strength http://www.slideshare.net/CsillaEgri/presentations Neurotrasnsmiter Introduction-cellular base-synapse51 • Present in presinaptic neuron • Releasd into the synaptic cleft due to depolarization of presynaptic neuron (Ca2+ dependent mechanism) • Specific receptor has to be present in postsynaptical membrane http://www.slideshare.net/CsillaEgri/presentations Neurotrasnsmiter Introduction-cellular base-synapse52 • Present in presinaptic neuron • Releasd into the synaptic cleft due to depolarization of presynaptic neuron (Ca2+ dependent mechanism) • Specific receptor has to be present in postsynaptical membrane http://www.slideshare.net/CsillaEgri/presentations Neurotrasnsmiter Introduction-cellular base-synapse53 • Present in presinaptic neuron • Releasd into the synaptic cleft due to depolarization of presynaptic neuron (Ca2+ dependent mechanism) • Specific receptor has to be present in postsynaptical membrane http://www.slideshare.net/CsillaEgri/presentations Neuromuscular junction Introduction-cellular base-synapse54 https://classconnection.s3.amazonaws.com/754/flashcards/2034754/png/ch_7_pic_41349381290275.png Introduction-cellular base-synapse55 https://classconnection.s3.amazonaws.com/108/flashcards/956108/jpg/bookpic421333407057201.jpg 56 Introduction-cellular base-synapse http://www.compoundchem.com/2015/07/30/neurotransmitters/ 57 Introduction-cellular base-synapse http://www.compoundchem.com/2015/07/30/neurotransmitters/ Excitatory/inhibtory postsynaptic potencial Introduction-cellular base-synapse58 http://www.slideshare.net/drpsdeb/presentations Signal summation Introduction-cellular base-synapse59 http://www.slideshare.net/drpsdeb/presentations • Temporal • Spatial https://www.slideshare.net/drgabe/biological-psychology-synapses?from_action=save Signal summation Introduction-cellular base-synapse60 https://www.slideshare.net/drgabe/biological-psychology-synapses?from_action=save http://www.geon.us/Memory/images/Summation.jpg Synaptic convergence Introduction-cellular base-synapse61 http://www.slideshare.net/drpsdeb/presentations Average number of synapses in one neuronal cell in primates ✓ Primary visual cortex (area17) – aprox. 4 000 ✓ Primary motor cortex (area4) – aprox. 60 000 Synaptic divergence Introduction-cellular base-synapse62 http://www.slideshare.net/drpsdeb/presentations Introduction-cellular base-synapse63 Networking http://www.slideshare.net/drpsdeb/presentations Introduction-cellular base-synapse64 Networking http://www.slideshare.net/drpsdeb/presentations Introduction-cellular base-synapse65 Neurotransmission vs. Neuromodulation • Information transmission • Specific • Receptors – ion channels • Short duration – membrane potential changes • Regulation of NS activity • Diffuse (volume transmission) • Receptors – G-proteins • Longer duration - changes in synaptic properties Introduction-cellular base-synapse66 Neurotransmission vs. Neuromodulation • Information transmission • Specific • Receptors – ion channels • Short duration – membrane potential changes • Regulation of NS activity • Diffuse (volume transmission) • Receptors – G-proteins • Longer duration - changes in synaptic properties Introduction-cellular base-synapse67 Neurotransmission vs. Neuromodulation • Information transmission • Specific • Receptors – ion channels • Short duration – membrane potential changes • Regulation of NS activity • Diffuse (volume transmission) • Receptors – G-proteins • Longer duration - changes in synaptic properties Introduction-cellular base-synapse68 Neurotransmission vs. Neuromodulation • Information transmission • Specific • Receptors – ion channels • Short duration – membrane potential changes • Regulation of NS activity • Diffuse (volume transmission) • Receptors – G-proteins • Longer duration - changes in synaptic properties Acetylcholine Introduction-cellular base-synapse69 • Nucleus basalis (Meynerti) abd other nuclei • Nicotin receptors • Muscarin receptors http://www.slideshare.net/drpsdeb/presentations • Sleep/wake regulation • Cognitive functions • Behavior • Emotions Noradrenalin Introduction-cellular base-synapse70 • Locus coeruleus • Nuclei raphe caudalis • Vigilance • Responsiveness to unexpected stimuli • Memory • Learning http://www.slideshare.net/drpsdeb/presentations Dopamin Introduction-cellular base-synapse71 http://www.slideshare.net/drpsdeb/presentations • Nigrostriatal system – Movement – Sensory stimuli • Ventrotegmentno-mesolimbicfrontal system – Reward – Cognitive function – Emotional behavior • Tubero-infundibular system – Hypotalamic-pituatory regulation • D1 receptors – excitatory • D2 receptors - inhibitory Serotonin Introduction-cellular base-synapse72 http://www.slideshare.net/drpsdeb/presentations • Nuclei raphe rostralis • Nuclei raphe caudalis • Anxiety/relaxation • Impulsive behavior • Sleep Neuromodulatory systems Introduction-cellular base-synapse73 http://image.slidesharecdn.com/neuromodulationincogniti on-140119031056-phpapp02/95/neuromodulation-in- cognition-5-638.jpg?cb=1419657931 Neuromodulatory systems Introduction-cellular base-synapse74 http://ausm.org.uk/wp-content/uploads/2015/02/Dopamine_Norepinephrine_Serotonin.jpg