Nervous System I PDF

Physiology of the nervous system- Neurophysiology Objectives: Part 1: basic concepts in nerous system The Divisions of the nervous system. Central nervous system (CNS), Peripheral nervous system (PNS), sensory (afferent) nervous system, motor (efferent) nervous system, somatic nervous sy...

Physiology of the nervous system- Neurophysiology Objectives: Part 1: basic concepts in nerous system The Divisions of the nervous system. Central nervous system (CNS), Peripheral nervous system (PNS), sensory (afferent) nervous system, motor (efferent) nervous system, somatic nervous system, autonomic nervous system: sympathetic and parasympathetic nervous system Neuron, the structural unit of the nervous system. Types of neurons Glial cells and their function Resting membrane potential and action potential. Role of Na+, K+ and ion channels in generating an action potential Myelinated and unmyelinated nerve fibers Transmission of nerve impulse in myelinated and unmyelinated axons Synapse Synaptic transmission of nerve impulse Excitatory postsynaptic potential (EPSP). Inhibitory postsynaptic potential (IPSP). Spatial and temporal summation of postsynaptic potential Neurotransmitters Divergent and convergent pathway in the nervous system Part2: major structures of the central nervous system and their main function Spinal cord brain stem Thalamus and hypothalamus Cerebellum Cerebrum Part 3.The autonomic nervous system. Structural organization of sympathetic and parasympathetic systems and their function  Specific terms and keywords Neuron Neuro- – Neurology – Neurologist – Neuropathology/neuropathy – Neurophysiology – Neuroscience Resting membrane potential Ion channels. Voltage-gated ion channels Threshold Action potential/nerve signal/nerve impulse Action potential propagation/ transmission/conduction Synapse Synaptic transmission  Neurons and nervous systems in different phyla Nerve net (cnidarians: jellyfish, anemones, hydra) neurons are dispersed in a thin layer Centralized and cephalized nervous system (flatworm, squid) Ganglionic central nervous system (anthropods, annelids, molluscs) Columnar nervous system (vertebrates) – Nervous systems of all animals originate from ectoderm – Neurons of all animals are quite similar in their functional properties – Changes in evolutionary history of nervous systems: changes in the complexity of organization of neurons into systems, rather than changes in neurons themselves AHill, Wyse , Andersonn ingly. Aimal physiology. 2nd  The divisions of the nervous system central nervous system- CNS – Brain – Spinal cord peripheral nervous system- PNS – Nerve fibers: 12 pairs of cranial nerves , 31 pairs of spinal nerves – Ganglion/ganglia – 2 subdivions : Afferent /sensory division Efferent/motor division: – somatic motor nervous system: skeletal muscles – autonomic nervous system-ANS: smooth muscles, glands, heart muscle » sympathetic nervous system » parasympathetic nervous system Fig.7.1 C.L. Standfield.2011. Principles of Human Physiology, 4th edition.  Cellular components of the nervous system Neuron Glial cells (70-90%)  Neuron Neuron: – Cell body (soma): receive information nucleus, rough endoplasmic reticulum, free ribosomes (Nissl bodies) golgi apparatus, Mature neurons lack centrioles – Dendrites – Axon: send information Some mm ->1m Transport materials to presynaptic membrane neural impulse transmission: – Axon hillock – Axon terminal Mature neurons can not C.L. Standfield.2011. Principles of Human Physiology, 4th edition. divide  Structural classification of neurons C.L. Standfield.2011. Principles of Human Physiology, 4th edition.  Classification of neuron types Functional classification – afferent/sensory neuron – efferent/ motor neuron – interneuron Structural classification – unipolar neuron one axon sensory neuron – bipolar neuron one axon and one axon-like dendrite Sensory neuron in the eyes, roof of the nasal cavity, and inner ear – multipolar neuron Many dendrites and one axon Interneuron and motor neuron  Neuroglia (glial cells) Rudolf Virchow (1821-1902) coined the term (1846) Large number (75-90% cells of the CNS, >1/2 brain mass) Functions: – Structural/physical support to neurons – Metabolic support to neurons – Component of blood-brain barrier – Protection of neurons from pathogens and removal of dead neurons – Production of cerebrospinal fluid – Formation of myelin sheath surrounding axons Types of glial cells: + Astrocyte:CNS + Ependymal: CNS: cerebrospinal fluid + Microglia: macrophages differentiated in CNS, + Oligodendrocyte: CNS + Schwann cells: PNS C.L. Standfield.2011. Principles of Human Physiology, 4th edition.  Astrocyte and microglia www.physoc.org/.../article.asp?ARTICLE_ID=95 Astrocytes (star-shaped cells) Microglia - metabolic support to neuron: provide lactate and glycogen - component of the blood–brain barrier - regulate the external chemical environment of neurons: removal of excess ions (K+), recycling excess neurotransmitters - Direct neuron migration, modulate the growth of dendrites and axons -Remove excess neurotransmitters  Oligodendrocyte CNS Oligodendrocytes: -Forming myelin sheath surrounding axons in the CNS - Cytoplasmic processes of one cell wrapping/surrounding several axons homepage.psy.utexas.edu/.../Cells/Cells.html  Schwann cells PNS fig.cox.miami.edu/.../neuro/neurophysiology.htm Forming myelin sheath surrounding axons in the PNS One Schwann cell forms one myelin sheath surrounding a small portion of an axon Myelinated axons: myelin sheath and nodes of Ranvier Unmyelinated axons a series of Schwann cells cover the length of several axons abutting Schwann cells are tightly joined -> no Ranvier nodes Axons invaginate Schwann cells plasma membrane Axons are connected to extra cellular fluid through channels  How do neurons function? Receive information (dendrites) Integrate information (cell body) Send information (axon): + down along the axon + out to other neurons information = electrical signal C.L. Standfield.2011. Principles of Human Physiology, 4th edition. Electrical properties of living cells -Negatively and positively charged ions -Negatively and positively organic molecules -Ion channels -Permeability of membrane for ions  Localization of ion channels in neurons Each region (in a neuron) has specific types of ion channels Most of the ion channels are gated (can open or close) The opening or closing of ion channels changes the permeability of the plasma membrane for a specific ion leading to a change in electrical properties of the cell or the release of neurotransmitters. Leak channels (none gated channels): always open, found throughout a neuron -> resting membrane potential Ligand-gated channels: open or close in response to the binding of a chemical messenger to a specific receptor in the plasma membrane Voltage-gated channels: open or close in response to changes in membrane potential: – voltage-gated Na+ and K+ channels mostly found in axon and axon hillock – Ca2+ channels in axon terminals  Resting membrane potential of a neuron A cell at rest has a potential difference across its membrane: inside of the cell is negative charge (relative to the outside): resting membrane potential (resting Vm) For a neuron Vm= -70mV Membrane potential is defined as the potential inside the cell relative to outside Neuron communicate by generating electrical signals in the form of changes in membrane potential. Some of these changes in membrane potential trigger the release of neurotransmitters which then carries signal to another cells. – What causes the resting membrane potential ? – What causes the membrane potential to change ?  What causes the resting membrane potential? solute ICF (mM) ECF (mM) K+ 140 4.0 Na+ 15.0 145.0 Cl- 4.0 115.0 Concentration gradients (created by Na+/K+ pump) of ions (sodium and potassium ions) across the plasma membrane The presence of ion channels (leaking channels) in the plasma membrane (mainly K+ channels when cells are at rest) The differences in the permeability of the plasma membrane to these 2 ions Chemical and electrical forces for moving sodium and potassium ions across the plasma membrane  Establishing a steady-state resting membrane potential Fig.7.8 C.L. Standfield.2011. Principles of Human Physiology, 4th edition.  Nernst Equation : to calculate the equilibrium potential across a cell’s membrane for one ion given its concentrations inside and outside the cell are known Ei: equilibrium potential for ion I Z: the valence of the ion (I)o: Concentration of I ion outside the cell (I)i: concentration of I ion inside the cell C.L. Standfield.2011. Principles of Human Physiology, 4th edition.  Goldman-Hodgkin-Katz (GHK) Equation To calculate membrane potential in case only K+ and Na+ are permeant and their concentration inside and outside the cell are known Electrical signal: changes in membrane potential Gated-ion channels open or close in response to a stimuli -> change the membrane permeability for ions -> change in membrane potential  Change in membrane potential is defined based on the direction of change relative to the resting membrane potential hyperpolarization a change to more negative value: Depolarization: a change to less negative/positive value Repolarization: potential returns to the resting membrane potential following a depolarization AHill, Wyse , Andersonn. Aimal physiology. 2nd e,2008.  Neurons communicate via 2 types of electrical signals Graded potentials Action potentials  Graded potentials Graded potentials are small changes in the membrane potential (Vm) Fig.7.12 C.L. Standfield.2011. Principles of Human Physiology, 4th edition. in response to a stimulus  Graded potential is decremental A graded potential dissipates as it moves to adjacent areas of the plasma membrane C.L. Standfield.2011. Principles of Human Physiology, 4th edition.  Graded potentials can sum temporally and spatially. The sum may reach the threshold for triggering an action potential C.L. Standfield.2011. Principles of Human Physiology, 4th edition. Action potentials (AP) result from changes in membrane permeabilities to ions AP results from three overlapping permeability changes: 1. increased permeability to Na+ by the rapid opening of voltage-gated Na+ channels 2. Decreased permeability to Na+ by inactivation of Na+ channels 3. Increased permeability to K+ by the the slower opening of voltage-gated K+ channels AHill, Wyse , Andersonn. Aimal physiology. 2nd e,2008.  Action potentials result from changes in membrane permeabilities to ions Action potential (AP) occurs in response to the graded potentials that reach the threshold. The threshold potentials act on voltage-gated sodium and potassium channels making them open or close Depolarization (membrane potential changes from -70 to +30mV: due to sudden and dramatic increase in permeability to sodium-> increase Na+ movement into the cell Fig.7.14 Repolarization: membrane potential returns (from +30mV) back to -70mV: Na+ permeability decrease, K+ permeability increases: K+ move out of the cell After-hyperpolarization: permeability of K+ remains high for a brief time (5-15 msec) after the membrane potential reaches the resting membrane potential Initiation of APs follows the all-or-none principle: whether a membrane is depolarized to threshold or above, the amplitude of the resulting action potential is Fig.7.17 the same; if the membrane is not depolarized to threshold, C.L. Standfield.2011. Principles of Human Physiology, 4th edition. no action potential occurs.  Refractory period During and immediately after an action potential (AP), the membrane is less excitable than it is at rest -> refractory period During absolute refractory period, no second AP is generated, regardless of the strength of the second stimulus During relative refractory period, a second AP can be generated but only when the second stimulus is stronger than needed to get Fig. 7.18 C.L. Standfield.2011. Principles of Human Physiology, 4th edition. threshold potential in resting conditions C.L. Standfield.2011. Principles of Human Physiology, 4th edition. C.L. Standfield.2011. Principles of Human Physiology, 4th edition.  Action potential propagation in unmyelinated axon Neural signal: action potential Continuous conduction SLOW Fig. 7.20 C.L. Standfield.2011. Principles of Human Physiology, 4 th edition.  Action potential propagation in unmyelinated axon Neural signal: action potential Saltatory conduction FAST Fig. 7.21 C.L. Standfield.2011. Principles of Human Physiology, 4 th edition. Classification of nerve fibers Based on conduction velocities of nerve signal of the nerves These conduction velocities depend on diameter of the nerves and the presence of myelin in the nerves Myelinated nerves with largest diameter have highest conduction velocities  Neurotoxins Neurotoxins are toxins interfering with normal function of the nervous system Some affecting ion channels Tetrodotoxin (TTX) from blowfish/puffer fish, saxitoxin (STX) from some marine dinoflagellate and a freshwater cyanobacterium, toxic at nanomolar concentrations – TTX blocks voltage-gated Na+ channels C.L. Standfield.2011. Principles of Human Physiology, 4th edition. Signal transmission between neurons: synaptic transmission  Synapse A specialized site of communication btw. 2 neurons, btw a neuron and an effector, or btw. a nonneural sensory cell and a neuron C.L. Standfield.2011. Principles of Human Physiology, 4th edition.  Types of synapses Electrical synapses: gap junction made by protein channels bridging the gap between two cells – Transmit signals instantaneously Chemical synapses – Ionotropic chemical synapses – Metabotropic chemical synapses  Structure of a chemical synapse Presynaptic neuron, synaptic knob Synaptic vesicles contain neurotransmitters Voltage-gated Ca2+ channels Synaptic cleft Post synaptic neuron, postsynaptic membrane Receptors on the postsynaptic membrane Fig.8.2 C.L. Standfield.2011. Principles of Human Physiology, 4th edition.  Chemical synaptic transmission 1. Stimulus = action potential 2. action potential -> Ca2+ channels open, Ca2+ move into presynaptic knob 3. Ca 2+ enters the cell and triggers the release of neurotransmitter by exocytosis 4. Neurotransmitter diffuses across the synaptic cleft, binding to receptors on the postsynaptic membrane 5. Cell responses 6. Some neurotransmitter is degraded by enzymes 7. Some neurotransmitter is taken up by the presynaptic cell 8. Some neurotransmitter diffuses away from the synaptic cleft Fig.8.2 C.L. Standfield.2011. Principles of Human Physiology, 4th edition.  Ionotropic chemical synapses release neurotransmitters binding to ionotropic receptors (channel-link receptors) The receptor is also an ion channel (ligand- gated ion channel) Neurotransmitter binds to receptor -> ion channel opens-> ion movement through postsynaptic membrane -> postsynaptic potential (PSP) Fast response (few msec) Fig.8.3.C.L. Standfield.2011. Principles of Human Physiology, 4th edition.  Metabotropic chemical synapses release neurotransmitters binding to metabotropic receptor ( G-protein linked receptor) (Cellular metabolism, gene expression) Fig.8.3 C.L. Standfield.2011. Principles of Human Physiology, 4th edition. G-protein-regulated ion channels respond to the binding of neurotransmitter slowly (msec-hours). Slow response  Excitatory and Inhibitory neurons Neuron releases neurotransmitters causing depolarization of postsynaptic membrane (Na+ move into the cell) -> EPSP- excitatory postsynaptic potential) -> Excitatory neuron-> - + excitatory synapse Neuron releases + - neurotransmitters causing hyperpolarization) of postsynaptic membrane (K+ move in or Cl- move out of the cell)- IPSP- inhibitory postsynaptic potential ->Inhibitory neuron-> inhibitory synapse Modified from: http://www.nature.com/neuro/journal/v6/n11/images/nn1103-1121-F1.jpg One neurotransmitter may mediate different postsynaptic actions through different postsynaptic receptors Acetycholine – binds ligand-gated channels/ ionotropic receptor mediating EPSPs in skeletal muscles – binds G-protein coupled receptor/ metabotropic receptor generating IPSPs in heart muscles  Neural integration: One neuron may contact many other neurons through its collaterals - divergent pathway Fig. 8.7.C.L. Standfield.2011. Principles of Human Physiology, 4th edition.  Neural integration: one neuron can receive information from many other neurons - Convergent pathway Fig.8.7 C.L. Standfield.2011. Principles of Human Physiology, 4th edition.  Spatial and temporal summation of postsynaptic potentials EPSPs and IPSPs are graded potentials, thus they can summate temporally and spatially Axon hillock acts as an integrator for the summation Fig.8.8 C.L. Standfield.2011. Principles of Human Physiology, 4th edition.  Neurotransmitters (NTs) C.L. Standfield.2011. Principles of Human Physiology, 4th edition. Most synapses in the CNS use amino acid neurotransmitters. Most fast EPSPs result from glutamate, most fast IPSPs from GABA or glycine Biogenic amines are found in few neurons but these neurons have widely projecting endings. Many receptors for these NTs have slow actions that modulate neuronal activities, rather than mediating fast excitation or inhibition Peptides are present in substantial minorities of CNS neurons. A neuroactive peptide may be co-released with one or more small molecule neurotransmitters and may function as a cotransmitter with slow synaptic effects.  Neurotransmitters (NTs) and drug’s target chemical messenger/neurotransmitter- receptor binding: potential target for a drug: - Morphine as pain killer - Glutamate: excitatory neuron - Serotonin and depression - Benzodiazepines (as Valium), sleeping aids (zolpidem), Alcohol and anxiety (enhance action of GABA) Fig.8.2 C.L. Standfield.2011. Principles of Human Physiology, 4th edition.  Neurons are organized into functional circuits in the nervous systems The functions of a nervous system depend on “wiring” – the anatomical organization by which neuron are connected into circuits. Behavioral activity is a property of the neural circuit that mediates it Startle response in cockroach Hill.Wyse.Anderson. Animal physiology.2e.Sinauer Associates, 2008 Questions: 1. Draw a typical neuron and label the main structures, list the functions of each structure 2. If an anion is located in greater concentration outside the cell compared to inside, would the equilibrium potential for that anion be positive, negative or zero? Explain it. 3. Explain ionic basic of an action potential 4. Explain why myelinated axons conduct action potential faster than unmyelinated axons? 5. Explain why the transmission of action potential in axon is not bidirectional? 6. Draw a typical chemical synapse, label the main structures, list the functions of each structure 7. Describe the sequence of events occuring at a chemical synapse 8. Explain ionic basic of an EPSP 9. Compare and contrast the events caused by the binding of neurotransmitters to ionotropic and metabotropic receptors