BIOH111. o Cell Module o Tissue Module o Integumentary system o Skeletal system o Muscle system o Nervous system o Endocrine system

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1 BIOH111 o Cell Module o Tissue Module o Integumentary system o Skeletal system o Muscle system o Nervous system o Endocrine system Endeavour College of Natural Health endeavour.edu.au 1

2 Textbook and required/recommended readings o Principles of anatomy and physiology. Tortora et al; 14 th edition: Chapter 12 Endeavour College of Natural Health endeavour.edu.au 2

3 BIOH111 NERVOUS SYSTEM MODULE o Session 15 (Lectures 27 and 28) Organisation and histology of the nervous system o Session 16 (Lectures 29 and 30) Function of neurons: conduction of nerve impulses o Session 17 (Lectures 31 and 32) CNS: Brain anatomy and function o Session 18 (Lectures 33 and 34) Sensations and special senses o Session 19 (Lectures 35 and 36) Spinal cord anatomy and physiology o Session 20 (Lectures 37 and 38) Spinal nerves and somatic sensory and motor pathways o Session 21 (Lectures 39 and 40) Autonomic nervous system: anatomy and function Endeavour College of Natural Health endeavour.edu.au 3

4 BIOH111 Lectures 29 and 30 Function of neurons: conduction of nerve impulses Department of Bioscience endeavour.edu.au

5 Lecture 29: Objectives Generation and propagation of nerve impulses Describe structure and functions ion channels involved Understand the effects of stimulus intensity on initiation of nerve impulse Describe steps in generating graded and action potentials, including membrane potential differences achieved by specific ion channels Propagation of nerve impulses Define differences between saltatory and continuous conduction, including the speed of nerve conduction propagation, by integrating the structure of a neuron Lecture 30: Downstream effects of action potential Define differences between electrical and chemical synapses and describe role of neurotransmitters in initiation of postsynaptic potentials Define and understand differences between excitatory and inhibitory post synaptic potentials Neurogenesis and neuronal repair Endeavour College of Natural Health endeavour.edu.au 5

6 FUNCTION OF NEURONS o Neurons receive stimulus, convert it to an electrical signal which is then conducted down the axon to a specific effector. neurons are electrically excitable due to the voltage difference across their membrane o Communicate with 2 types of electric signals 1. graded potentials: local membrane changes only 2. action potentials: travel long distances Endeavour College of Natural Health endeavour.edu.au 6

7 ION CHANNELS o In living cells, a flow of ions occurs through ion channels in the cell membrane. 2 types: 1. non-gated (leak) channels are always open nerve cells have more K + than Na + leakage channels as a result, membrane permeability to K + is higher explains resting membrane potential of -70mV in nerve tissue 2. gated channels open and close in response to a stimulus results in neuron excitability respond to voltage changes, ligands and mechanical pressure (voltage-, ligand- and mechano-gated channels) Endeavour College of Natural Health endeavour.edu.au 7

8 Gated Ion Channels Where have you encountered a ligandgated channel before? Endeavour College of Natural Health endeavour.edu.au 8

9 RESTING MEMBRANE POTENTIAL -70mV o Definition: negative ions build up along inside & positive ions along outside of the cell membrane (note: cytosol of the cell is electrically neutral); cell is polarized o Different cell types have different resting membrane potential; neurons: -70 mv (inside of a cell is more negative) Endeavour College of Natural Health endeavour.edu.au 9

10 RESTING MEMBRANE POTENTIAL 3 factors contributing to negative resting membrane potential: 1. Unequal distribution of ions across the membrane mediated by the K+ leak channel 2. Anions can not exit the cell 3. Na+/K+ ATPase expels 3 Na+ ions for every 2 K+ ions transported into the cell Endeavour College of Natural Health endeavour.edu.au 10

11 GRADED POTENTIAL (GP) o Small deviations from resting potential of -70mV hyperpolarization = membrane has become more negative depolarization = membrane has become more positive o The signals are graded - depending on the strength of the stimulus the GP varies in amplitude (size); localized o 2 types: postsynaptic GP occurs in dendrites or cell body in response to neurotransmitters receptor/generator GP occur in sensory neurons in response to sensory receptor stimulation Endeavour College of Natural Health endeavour.edu.au 11

12 GP STIMULUS STRENGTH AND SUMMATION The amplitude of a graded potential depends on the stimulus strength» no further action from neuron Graded potentials can be added together to become larger in amplitude» can initiate action potential if -55mV (threshold) or above (supratheshold) is reached

13 ACTION POTENTIAL o Series of rapidly occurring events that change and then restore the membrane potential of a neuronal membrane. o Achieved by opening/closing sequence of voltage-gated ionchannels: Na + in (depolarization), K + out (repolarization) o All-or-none principle: when stimulus reaches a threshold AP is always same (stronger stimulus will not cause a larger impulse) o Travels over surface of axon without dying out Let s break it down Endeavour College of Natural Health endeavour.edu.au 13

14 DEPOLARIZING PHASE -70mV -55mV +30mV o Stimulus: chemical or mechanical; causes graded potential to reach at least -55mV (threshold) o Voltage-gated Na + channels open & Na + rushes into cell in resting membrane, inactivation gate of sodium channel is open & activation gate is closed (Na + can not get in) when threshold (-55mV) is reached, both open & Na + enters inactivation gate closes again in few tenthousandths of second o Net effect: change in the membrane potential up to +30mV Endeavour College of Natural Health endeavour.edu.au 14

15 REPOLARIZING PHASE +30mV -90mV -70mV o At -55mV voltage-gated K + channels open (much slower than Na + channel opening) when K + channels finally do open, the Na + channels have already closed (Na + inflow stops) o K + outflow returns membrane potential to -70mV After-hyperpolarizing phase - if enough K + leaves the cell, it will reach a -90mV membrane potential and K + channels close o Net effect: membrane potential returns to the resting potential of -70mV Endeavour College of Natural Health endeavour.edu.au 15

16 REFRACTORY PERIOD OF ACTION POTENTIAL Definition: period of time during which neuron can not generate another action potential. o Absolute refractory period even very strong stimulus will not begin another AP inactivated Na + channels must return to the resting state before they can be reopened large fibers have absolute refractory period of 0.4 msec and up to 1000 impulses per second are possible o Relative refractory period a suprathreshold stimulus only will be able to start an AP K + channels are still open, but Na + channels have closed Endeavour College of Natural Health endeavour.edu.au 16

17 AP SUMMARY Resting membrane potential = -70mV Depolarization: -70mV +30 mv Repolarization: +30 mv -70 mv Endeavour College of Natural Health endeavour.edu.au 17

18 PROPAGATION OF ACTION POTENTIAL o An action potential spreads (propagates) over the surface of the axon membrane as Na+ flows into the cell during depolarization, the voltage of adjacent areas is effected and their voltage-gated Na+ channels open self-propagating along the membrane o The traveling action potential is called a nerve impulse Endeavour College of Natural Health endeavour.edu.au 18

19 CONTINUOUS vs SALTATORY CONDUCTION o Continuous conduction unmyelinated fibers name the nervous system division where these fibers are represented step-by-step depolarization of each adjacent portion of the length of the axon plasma membrane Endeavour College of Natural Health endeavour.edu.au 19

20 CONTINUOUS vs SALTATORY o Saltatory conduction CONDUCTION depolarization only at nodes of Ranvier where there is a high density of voltagegated ion channels - name the nervous system division where myelinated fibers are represented current carried by ions flows through extracellular fluid from node to node Endeavour College of Natural Health endeavour.edu.au 20

21 Structure-function relationship: Thinking about the 2 conduction processes and the neurons and neuronal function they occur in, comment on why this division is observed. Endeavour College of Natural Health endeavour.edu.au 21

22 SPEED OF IMPULSE PROPAGATION o The propagation speed of a nerve impulse is not related to stimulus strength. 3 factors that affect speed of propagation: 1. Myelination AP travels more rapidly through myelinated fibres 2. Temperature AP travels more rapidly when temperature is higher 3. Axon diameter AP travels more rapidly through larger fibres; 3 fiber types: A fibers: largest (5-20 microns & 130 m/sec); e.g. myelinated somatic sensory & motor to skeletal muscle B fibers: medium (2-3 microns & 15 m/sec); e.g myelinated visceral sensory & autonomic preganglionic C fibers: smallest ( microns & 2 m/sec); e.g. unmyelinated sensory & autonomic motor Endeavour College of Natural Health endeavour.edu.au 22

23 BIG PICTURE REVISION In lectures 27 and 28 we have covered how the nervous system is structured and described the cellular components of the nervous system. In lectures 29 and 30 we are discussing the function of the nervous system nerve impulse initiation, conduction and effect. While going through the lectures always ask yourself: - why is this function applicable to this structure and not the other come back to structure-function relationship - while steps are important, think about WHY specific things are happening (e.g. why in depolarisation system you have an increase in membrane potential?; what is membrane potential?..) this will help you remember the steps. Endeavour College of Natural Health endeavour.edu.au 23

24 A) Think about nerve impulse physiology initiated by sensory neurons after light and firm touch. How do we differentiate between these two touches? B) Investigate effect of local anaesthetics (botox, novocain, lidocaine) on nerve impulse conduction and comment: 1. Where in the nerve conduction process do they act? 2. What is the overall effect of local anaesthetics on nerve impulse conduction? 3. Why do we have different anaesthetics? Endeavour College of Natural Health endeavour.edu.au 24

25 Lecture 29: Objectives Generation and propagation of nerve impulses Describe structure and functions ion channels involved Understand the effects of stimulus intensity on initiation of nerve impulse Describe steps in generating graded and action potentials, including membrane potential differences achieved by specific ion channels Propagation of nerve impulses Define differences between saltatory and continuous conduction, including the speed of nerve conduction propagation, by integrating the structure of a neuron Lecture 30: Downstream effects of action potential Define differences between electrical and chemical synapses and describe role of neurotransmitters in initiation of postsynaptic potentials Define and understand differences between excitatory and inhibitory post synaptic potentials Neurogenesis and neuronal repair Endeavour College of Natural Health endeavour.edu.au 25

26 SYNAPSES o Definition: synapse is the functional junction between neurons or between a neuron and an effector (muscle or gland). o 2 types: electrical chemical Endeavour College of Natural Health endeavour.edu.au 26

27 ELECTRICAL SYNAPSE o Ionic current spreads to next cell through gap junctions no signal conversion o Faster, two-way transmission & capable of synchronizing groups of neurons o e.g. cardiac muscle and visceral smooth muscle Endeavour College of Natural Health endeavour.edu.au 27

28 CHEMICAL SYNAPSE o One-way information transfer from presynaptic neuron to postsynaptic neuron or effector o AP reaches end bulb voltagegated Ca +2 channels open Ca +2 flows inward release of neurotransmitter into synaptic cleft binding of neurotransmitter to ligand-gated receptors EPSP/IPSP o Signal conversion: electrical chemical (pre) then chemical electrical (post) Name and describe a process you already know that uses this sequence of events. Endeavour College of Natural Health endeavour.edu.au 28

29 NEUROTRANSMITTERS Small-molecule: Excitatory and inhibitory chemicals secreted by neurons to act on neurons; present in both CNS and PNS; some both excitatory and inhibitory Neuropeptides: Small proteins secreted by neurons to act on neurons Endeavour College of Natural Health endeavour.edu.au 30

30 NEUROTRANSMITTERS (small molecule class) o Acetylcholine (ACh) released by many PNS neurons & some CNS Function: learning and memory; activates muscle action; awakening and attention excitatory on NMJ but inhibitory at others inactivated by acetylcholinesterase Endeavour College of Natural Health endeavour.edu.au 31

31 NEUROTRANSMITTERS (small molecule class catecholamines) o Dopamine o Structure: monoamine; synthesised from Phenylalanine o Released by CNS neurons o Function: regulating skeletal muscle tone (movement); pleasure and addiction o inhibitory Endeavour College of Natural Health endeavour.edu.au 32

32 NEUROTRANSMITTERS o Norepinephrine or noradrenaline (NE) Structure: monoamine, synthesized from dopamine Released by CNS and ANS neurons Function: regulates mood, dreaming, awakening from deep sleep Excitatory and inhibitory o Epinephrine or adrenaline Structure: monoamine, synthesized from dopamine Released by CNS and ANS neurons Function: increases blood flow and heart rate; awareness Excitatory and inhibitory NOTE: both are also hormones and secreted by adrenal medulla Endeavour College of Natural Health endeavour.edu.au 33

33 NEUROTRANSMITTERS (small molecule class indolamines) o Serotonin (5-HT) Structure: monoamine, synthesized from tryptophan Released by CNS neurons and enterochromaffin cells (90%; endocrine cells not neural cells) Function: control of mood, temperature and appetite regulation, & induction of sleep inhibitory Endeavour College of Natural Health endeavour.edu.au 34

34 NEUROTRANSMITTERS (amino acid class) o Glutamate (Glu) Structure: essential amino acid Released by nearly all excitatory neurons in the brain Function: learning and memory; regulates development of new nerve contacts excitatory o GABA Structure: zwitterion; synthesized from glutamate Released only in CNS Function: calms firing in CNS; contributes to muscle control inhibitory Endeavour College of Natural Health endeavour.edu.au 35

35 NEUROTRANSMITTERS (neuropeptides class) o Endorphins Structure: peptide; opioid Released in both CNS and PNS Function: potent analgesic (pain-relieving); improved memory and learning; pleasure and euphoria generally inhibitory o Substance P Structure: peptide Released in both CNS and PNS ( from peripheral pain receptors to CNS); can act as a hormone in GI tract Function: enhances our perception of pain excitatory NOTE: acupuncture may produce loss of pain sensation because of release of opioids-like substances such as endorphins. Endeavour College of Natural Health endeavour.edu.au 36

36 NEUROTRANSMITTERS o ATP and other purines Small molecule class excitatory in both CNS & PNS released with other neurotransmitters (ACh & NE) e.g. ADP, AMP & adenosine o Gases Structure: synthesised from amino acid arginine (formed on demand and acts immediately) diffuses out of cell that produced it to affect neighboring cells Function: may play a role in memory & learning; vasodilator that helps lower blood pressure e.g. nitric oxide Endeavour College of Natural Health endeavour.edu.au 37

37 CHEMICAL SYNAPSE o One-way information transfer from presynaptic neuron to postsynaptic neuron or effector o AP reaches end bulb voltagegated Ca +2 channels open Ca +2 flows inward release of neurotransmitter into synaptic cleft binding of neurotransmitter to ligand-gated receptors EPSP/IPSP o Signal conversion: electrical chemical (pre) then chemical electrical (post) Endeavour College of Natural Health endeavour.edu.au 39

38 Effector side of nerve conduction EXCITATORY & INHIBITORY POTENTIALS o The effect of a neurotransmitter on the postsynaptic terminal/effector can be either excitatory or inhibitory: 1. Excitatory postsynaptic potentials (EPSP) Structure: mediated by ionotropic receptors; net effect: results from the opening of ligand-gated cation channels Function: depolarizing postsynaptic cell is more likely to reach threshold Endeavour College of Natural Health endeavour.edu.au 40

39 Effector side of nerve conduction EXCITATORY & INHIBITORY POTENTIALS 2. Inhibitory postsynaptic potential (IPSP) Structure: mediated by ionotropic and metabotropic receptors; net effect: results from the opening of ligand-gated Cl- or K+ channels Function: postsynaptic cell becomes more negative or hyperpolarized postsynaptic cell is less likely to reach threshold Endeavour College of Natural Health endeavour.edu.au 41

40 Quick recap Mediated by ionotropic receptors only Mediated by ionotropic or metabotropic receptors Endeavour College of Natural Health endeavour.edu.au 42

41 MODIFYING CHEMICAL SYNAPSE o Neurotransmitter effects can be modified: synthesis can be stimulated or inhibited release can be blocked or enhanced removal can be stimulated or blocked 3 ways of neurotransmitter removal: 1. Diffusion - move down concentration gradient 2. Enzymatic degradation - e.g. acetylcholinesterase 3. Uptake by neurons or glial cells e.g. neurotransmitter transporters Prozac: serotonin reuptake inhibitor o Receptors can be modified: 1. Agonist - anything that enhances the action of a neurotransmitter 2. Antagonist - anything that blocks the action of a neurotransmitter XX Why is removal of neurotransmitters important?? What would happen if they weren t removed? What happens in the presence of Prozac? Endeavour College of Natural Health endeavour.edu.au 43

42 NERVE vs MUSCLE ACTION POTENTIALS Nerve Muscle Resting membrane potential -70mV -90mV Duration ms 1-5 ms skeletal ms cardiac and smooth Structure Axon only Entire muscle fibre membrane Endeavour College of Natural Health endeavour.edu.au 44

43 SUMMATION o Definition: summation is a addition of all nerve impulses received by one neuron; occurs when several presynaptic end bulbs release their neurotransmitters at about the same time o important in neural circuits o 2 types: spatial and temporal Purves D et al, Neuroscience, 2 nd addition. Endeavour College of Natural Health endeavour.edu.au 45

44 SPATIAL SUMMATION o Summation of effects of neurotransmitters released from several end bulbs onto one neuron o Same time different locations Endeavour College of Natural Health endeavour.edu.au 46

45 TEMPORAL SUMMATION o Summation of effect of neurotransmitters released from 2 or more firings of the same end bulb in rapid succession onto a second neuron o Different times same location Endeavour College of Natural Health endeavour.edu.au 47

46 Work in groups of 3-4 and identify processes you learned about in each of the spots labelled 1-6. HINT: you may not be able to identify all points (will use this in later sessions) Endeavour College of Natural Health endeavour.edu.au 48

47 In spinal cord, Renshaw cells normally release an inhibitory neurotransmitter (glycine) onto motor neurons preventing excessive muscle contraction. Strychnine binds to and blocks glycine receptors in the spinal cord. Applying the knowledge of nerve impulse conduction and muscle contraction comment on strychnine mode of action and the overall systemic result. If this was an exam question how would you answer? Endeavour College of Natural Health endeavour.edu.au 49

48 PLASTICITY & REPAIR o Plasticity maintained throughout life sprouting of new dendrites synthesis of new proteins changes in synaptic contacts with other neurons o Limited ability for repair PNS can repair damaged dendrites or axons CNS repairs are possible but extremely limited (research ongoing) Neuman et al, 2014 Endeavour College of Natural Health endeavour.edu.au 50

49 REPAIR WITHIN THE PNS o Axons & dendrites may be repaired if neuron cell body remains intact Schwann cells remain active and form a tube scar tissue does not form too rapidly o hours : Chromatolysis; Nissl bodies break up into fine granular masses o 3-5 days: Wallerian degeneration occurs (breakdown of axon & myelin sheath distal to injury) retrograde degeneration occurs back one node o Within several months, regeneration occurs neurolemma on each side of injury repairs tube (Schwann cell mitosis) axonal buds grow down the tube to reconnect (1.5 mm per day) Endeavour College of Natural Health endeavour.edu.au 51

50 NEUROGENESIS IN THE CNS o Formation of new neurons from stem cells was not thought to occur in humans 1992 a growth factor was found that stimulates adult mice brain cells to multiply 1998 new neurons found to form within adult human hippocampus (area important for learning) o There is a lack of neurogenesis in other regions of the brain and spinal cord. o Factors preventing neurogenesis in CNS inhibition by neuroglial cells, absence of growth stimulating factors, lack of neurolemmas, and rapid formation of scar tissue Endeavour College of Natural Health endeavour.edu.au 52

51 Clinical applications: MULTIPLE SCLEROSIS (MS) o Autoimmune disorder causing destruction of myelin sheaths in CNS sheaths becomes scars or plaques 1/2 million people in the United States appears between ages 20 and 40 females twice as often as males o Symptoms include muscular weakness, abnormal sensations or double vision o Remissions & relapses result in progressive, cumulative loss of function Endeavour College of Natural Health endeavour.edu.au 53

52 Clinical applications: EPILEPSY o The second most common neurological disorder affects 1% of population o Characterized by short, recurrent attacks initiated by electrical discharges in the brain lights, noise, or smells may be sensed skeletal muscles may contract involuntarily loss of consciousness o Epilepsy has many causes, including; brain damage at birth, metabolic disturbances, infections, toxins, vascular disturbances, head injuries, and tumors Endeavour College of Natural Health endeavour.edu.au 54

53 COMMONWEALTH OF AUSTRALIA Copyright Regulations 1969 WARNING This material has been reproduced and communicated to you by or on behalf of the Endeavour College of Natural Health pursuant to Part VB of the Copyright Act 1968 (the Act). The material in this communication may be subject to copyright under the Act. Any further reproduction or communication of this material by you may be the subject of copyright protection under the Act. Do not remove this notice. Endeavour College of Natural Health endeavour.edu.au 55

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