Introduction

1. MBS 221Lecture 3: Refreshing prior knowledge about neurocytology and neurophysiologyDr R. McBrideDepartment of Medical BiosciencesUniversity of the Western CapeOffice number B5.1(021) 959-2333rmcbride@uwc.ac.zaConsultation hrs: Wed 11h00 – 13h00

2. before we can understand how networks of neurons produce motor behaviour, we must first refresh our memories regarding the properties of individual neurons the nervous system is the most organized and complex tissue known there are 1012 cells of the nervous system - the minority are neurons (10-20%) and the majority are glial cells neuronsare the structural and functional units of the nervous system - recall Santiago Ramon y Cajal’s ‘neuron doctrine’ Introduction

3. Introduction

4. despite their variety (over 50 distinct types), all neurons have common features that distinguish them from all other cells highly polarized used to restrict the flow of impulses in one direction compartmentalized cellular functions cell body/soma and dendrites - receive input axon - propagates electrical impulses terminals - output electrically and chemically excitable due to ion channels and pumps Introduction

5. Introduction • the structural and functional blueprint of neurons is similar to epithelial cells, from which they arise: • epithelial cells have basal-apical polarity • the epithelial cell’s basolateral surface corresponds to the basal aspect of the neuron where the dendrites emerge from • the epithelial cell’s apical surface corresponds to the apical aspect of the neuron where the axon emerges from • the vacuolar apparatus (membrane system) corresponds to all the membranous organelles in the neuron’s cytoplasm - neurons have proximal-distal polarity which is equivalent to basal-apical polarity in epithelial cells • membranous organelles are selectively distributed throughout the neuron • specialized cytoskeletal elements, called microtubules, neurofilaments and microfilaments determine neuronal shape

6. Introduction The epithelial blue print of neurons

7. Introduction www.valdostamuseum.org

8. Introduction • most proteins are synthesized in the cell body • proteins and organelles are transported along the axon by means of microtubules and the motor molecule kinesin • fast axonal transport of membranous organelles in an anterograde (from cell body toward nerve endings) and retrograde (from nerve endings toward cell body ) direction at 200-400 mm/day • slow axonal transport of cytosolic and cytoskeletal proteins (e.g. the subunits of microtubules and neurofilaments) only occurs in an anterograde direction at <1-5 mm/day

9. Introduction

10. Types of neurons • neurons can be classified according to their structure, function, mode of action or length • structurally classified according to the number of processes extending from their cell body • multipolar • unipolar • pseudo-unipolar • bipolar • functionally classified according the direction in which the nerve impulse travels relative to the CNS: • sensory (afferent) • motor (efferent) • interneurons • classified according to mode of action: • excitatory • inhibitory • classified according to length: - long axons (Golgi type 1) and short axons (Golgi type II)

11. Types of neurons based on structure • multipolar neurons have three or more process, are the most common, and are the major neuron type in the CNS

12. Types of neurons based on structure • unipolar neurons are uncommon but form the parasympathetic portion of cranial nerves www.dkimages.com

13. Types of neurons based on structure • pseudo-unipolar neurons have a short single process that emerges from the cell body and divides T-like into proximal and distal branches, are found mainly in ganglia in the PNS where they function as sensory neurons Kierszenbaum

14. Types of neurons based on structure • bipolar neurons are uncommon and perform specialized functions Kierszenbaum

15. sensory neurons transmit impulses from the periphery to the CNS motor neurons transmit impulses from the CNS to the periphery interneurons transmit impulses within the CNS and are the most numerous, accounting for 99% of all neural types Types of neurons based on function

16. recall that these classifications “overlap”: below are all multipolar neurons that are also either motor neurons or interneurons Types of neurons based on function Golgi type II Golgi type I

17. Ion channels and pumps • neurons are surrounded by a plasma membrane, referred to as the plasmalemma, the structural basis of which is a phospholipid bilayer • repercussions for small/large molecules? • repercussions for lipid-soluble/lipid-insoluble molecules? • repercussions for uncharged/charged molecules? • hence the necessity for ion channels… • ion channels and pumps are two of the many types of functional proteins present in the plasmalemma - recall that the concentrations of the various ions are different extracellulary vs intracellularly • recall the major extracellular ion • recall the major intracellular ion • recall the major ion exchange pump

18. Ion channels www.unmc.edu

19. Ion pumps

20. Membrane potential • the difference in charge across the plasma membrane (due to the concentration gradients for the various ions) creates a potential difference/voltage across the plasmalemma called the membrane potential, which is measured in millivolts (mV)(1 mV = 0.001 V) • when a neuron is at rest (unstimulated), the membrane is at equilibrium i.e. there is no net transmembrane currents and the membrane potential is called the resting membrane potential (RMP) • recall that it is customary in neurophysiology to express the RMP as negative inside with respect to the outside • the average RMP measures -65 mV (-40 to -80 mV) - the RMP is the same throughout the neuron and is mainly due to the concentration difference for K+

21. an decrease/increase in RMP results in both local and propagated signals a decrease in RMP (-65 to -55 mV) = depolarization = excitatory an increase in RMP (-65 to 75 mV) =hyperpolarization= inhibitory depolarization and hyperpolarization are local potentials Membrane potential

22. Local signaling • electric signals occur in two forms: local potentials(nonpropagated)andaction potentials(propagated) • local potentials: • are small changes in membrane potential (depolarizations or hyperpolarizations) confined to small regions of the plasmalemma • caused by a stimulus (e.g. ligand-receptor binding, changes in charge across the membrane, mechanical stimulation, temperature changes or spontaneous changes in membrane permeability) applied at that location on the membrane • called “graded potentials” because a strong stimulus produces a greater potential change than a weaker one • can only function as signals over a very short distance because they are are conducted (spread) over the membrane in a decremental fashion – i.e. their magnitude (strength) rapidly deceases as they spread • can summate (or add to each other) if successive stimuli are applied before the local potential produced by the first stimulus has returned to the RMP • are  important because of their effect on the generation of action potentials • examples of local potentials are receptor potentials and synaptic potentials

23. local potentials are graded (a) note that the stronger the stimulus the larger the change in membrane potential (b) note that these potentials can summate, or add onto each other, increasing the likelihood that an action potential will be produced Local signaling

24. Propagated signaling • when a local potential causes depolarization of the membrane to a sufficiently less negative membrane potential (called the threshold), an action potential (AP) is produced • compared to local potentials, APs are a large change in the RMP that spreads over the entire surface of the cell • an AP is a single long-distance electrical impulse passing down an axon - an AP is an all or nothing phenomenon i.e. once the threshold stimulus intensity is reached, an AP will be generated • information in the nervous system is  coded the frequency of firing rather than the size of the AP • the AP has a depolarization phase, followed by a repolarization phase, and finally followed by an afterpotential (a slightly hyperpolarized phase)

25. Propagated signaling • during the depolarization phase - first partial, then rapid - of the AP, the membrane potential moves away from the RMP and the inside of the membrane becomes more positive because diffuses into the cell through voltage gated Na+ channels • during the repolarization phase of the AP, the membrane potential returns toward the RMP and the inside of the membrane becomes more negative because: • voltage-gated Na+ channels close and Na+ diffusion into the cell slows to resting levels • voltage-gated K+ channels continue to open and K+ diffuses out of the cell • during the afterpotential phaseof the AP, the membrane potential may be slightly hyperpolarized for a short period because voltage-gated K+ channels remain open for a short time - the original RMP is reestablished when these channels close

26. +40 Membrane potential (mV) [C] [B] 0 [A] [D] threshold -70 Time (msec) 0 1 2 3 Propagated signaling • an AP has four phases: 1. partial depolarization (local potential) A 2. rapid depolarization B 3. repolarization C 4. hyperpolarization (afterpolarization) D

27. Propagated signaling

28. Propagated signaling • during the absolute refractory period, the region of the membrane where the AP was produced becomes completely insensitive to further stimulation i.e. even if a 2nd stimulus, no matter how strong, arrives at that region, it can’t initiate another AP - occurs from the beginning of the AP (i.e. depolarization) until near the end of repolarization and  guarantees that: • once an AP has started, both the depolarization and repolarization phases will be completed before another AP can begin and • that a strong stimulus can’t lead to a prolonged depolarization of the membrane • the relative refractory period follows the absolute refractory period and is a time during which a stronger-than-threshold stimulus can evoke another AP i.e. a sufficiently strong stimulus can produce another AP after the absolute refractory period but before the relative refractory period is completed

29. Propagated signaling

30. Local vs propagated signaling

31. Local vs propagated signaling

32. Possible test/exam questions from this lecture… unless otherwise indicated: • all scanned images are from Kandel ER, Schwartz JH and Jessell TM. Principles of Neural Science. 4th International Edition. McGraw-Hill Companies, Inc. • Define/describe the following terms/concepts (2-5 marks): • microtubule, kinesin, neurofilament, microtubule, anterograde and retrograde transport, fast and slow axonal transport, multipolar, unipolar, pseudo-unipolar and bipolar neurons, sensory, motor and interneurons, excitatory and inhibitory neurons, Golgi type I and II neurons, plasmalemma, ion channels, ion pumps, sodium-potassium ATPase pump, membrane potential, millivolt, resting membrane potential, depolarization, hyperpolarization, local/graded potentials (receptor and synaptic potentials), propagated potentials, summation, threshold, action potential, all or nothing phenomenon, partial and rapid depolarization, repolarization and hyperpolarization/afterpotential phase, absolute and relative refractory period

33. Possible test/exam questions from this lecture… • Answer the following questions (5-10 marks): • describe the common features that all neurons share • describe the ‘epithelial blue print’ of neurons • describe the transport of proteins within neurons • describe the structural, function modal and length classification of neurons • discuss ion channels and ion pumps in the plasmalemma • describe the functioning of the sodium-potassium ATPase pump in the plasmalemma • discuss the establishment and maintenance of the resting membrane potential • describe the phases of an action potential • describe the absolute and relative refractory periods • compare local and propagated signals in terms of their amplitude, duration, summation, effect of signal and type of propagation • describe the monosynaptic stretch reflex with emphasis on the sequence of receptor, action and synaptic potentials