2. Computer Simulation of Neurophysiology Presented in Lab

3. Computer Simulation of Neurophysiology Action Potential Stimulation –Determine threshold –Observe effects of other stimuli Effects of Drugs Determination of Conduction Velocity

4. Action Potential Generation: Stimulus Action potentials are triggered by membrane depolarization at the axon hillock Depolarization caused by increased permeability to ions Permeability typically increased by chemically-or physically-gated ion channels Can also be affected by membrane perturbations, changes in ion gradients, etc.

5. Threshold and “All or None” Action potentials are driven by the opening of voltage-gated ion channels Require a minimum amount of depolarization for any to open = threshold Once some open, they in turn cause others to open “All or none” response for single neurons Stimulus Intensity Threshold Neuron Axon Response

6. Compound Action Potentials Extracellular recordings of whole nerve segments –Many axons w/ variable thresholds –Different degrees of stimulation Amplitude of Action Potential varies with stimulus strength Vary NUMBER of axons undergoing AP Does NOT violate “all or none” principle Action Potential Amplitude Stimulus Intensity

7. Compound Action Potentials Subthreshold stimulus –No AP Threshold stimulus –Minimal compound AP Submaximal stimulus –Variable number of axons undergo AP –Variable amplitude Maximal stimulus –Maximum amplitude –Does not vary with stim strength subtheshold threshold submaximal maximal Action Potential Amplitude Stimulus Intensity

8. Nerve signaling and drugs Signal conduction within a neuron occurs through action potentials –voltage-gated channels Signal conduction from one nerve to another occurs through synapses –Chemically gated channels Neurotoxins could affect nerve signaling at either site

9. Neurotoxins Affect voltage-gated ion channels (alter APs) –Tetradotoxin, novocain – block v.g. Na + channels –Scorpion venoms – keep Na + channels open and K + channels closed (prolonged depolarization) –Chlorform – open K + channels (hyperpolarization)

10. Neurotoxins Affect chemistry at synapses (alter normal AP-inducing stimuli) –Botulinum toxin (Botox) – prevents vesicle release from somatic motor neurons –Latrotoxin (Black widows) – triggers excessive vesicle release from somatic motor neurons –Cobratoxin (Cobras) – blocks nicotinic receptors

11. Factors Affecting Signal Conduction: Myelination myelin = lipid insulator –PM of Schwann cells or oligodendrocytes Signals “jump” from one node to the next (saltatory conduction) –  AP conduction speed http://www.blackwellscience.com/matthews/actionp.html

12. Factors Affecting Signal Conduction: Axon Diameter Cable Theory –resistance to current increases with decreased diameter –resistance slows current Therefore: –Conduction Velocity  1/Resistance –Diameter  1/Resistance –Conduction velocity  Diameter

13. Neurophysiology Background Material (Not Presented in Lab)

14. Resting Potential Inside of cell negative relative to the outside (-70 mV) [Na + ] higher outside than inside [K + ] higher inside than outside At RP, neither K + nor Na + are in equilibrium

15. Action Potentials begins at the axon hillock, travels down axon brief, rapid reversal of MP –Opening of voltage-gated Na + and K + channels Self propagating All or none

16. Action Potential Function (Depolarization) Triggering event causes membrane to depolarize slow increase until threshold is reached voltage-gated Na + channels open –Na + enters cell –further depolarization –more channels open –further depolarization membrane reverses polarity (+30 mV)

17. Action Potential Function (Repolarization) V.G. Na + channels close Delayed opening of V.G. K + channels –reach peak permeability as Na + channels close K + rushes out of the cell –membrane potential restored K + channels close [Na + ] and [K + ] restored by the Na + -K + pump

18. Cartoons! http://www.blackwellscience.com/m atthews/channel.html

19. Action Potentials AP duration ~ 1-2 ms response of the nerve cell to the stimulus is “all or none” –Amt of depolarization always the same –differences in stimulus intensity are detected by The number of neurons undergoing AP in response to the stimulus The frequency of action potential generation

20. Action Potential Propagation Na + moving into one segment of the neuron quickly moves laterally inside the cell Depolarizes adjacent segment to threshold http://www.blackwellscience.com/matthews/actionp.html

21. Chemical Synapses presynaptic neuron –synaptic terminal bouton –contains synaptic vesicles filled with neurotransmitter synaptic cleft –space in-between cells postsynaptic neuron –Subsynaptic membrane –Receptor proteins for neurotransmitter

22. Chemical Synapses AP in terminal opens Ca 2+ channels –Ca 2+ rushes in. Ca 2+ causes vesicles to fuse to PM and release contents Transmitter diffuses across synaptic cleft and binds to receptors on subsynaptic membrane

23. Chemical Synapses Specific ion channels in subsynaptic membrane open –chemically-gated ion channels Ions enter postsynaptic cell – graded potential forms If graded potential is strong enough to reach threshold, generates action potential in postsynaptic cell

24. Cartoon! http://www.blackwellscience.com/ma tthews/nmj.html

25. Types of Chemical Synapse Excitatory chemical synapse: –excitatory postsynaptic potentials (EPSPs) –Small depolarization of postsynaptic neuron closer to threshold http://www.blackwellscience.com/matthews/neurotrans.html

26. Types of Chemical Synapse Inhibitory chemical synapse: –inhibitory postsynaptic potentials (IPSPs) –Small hyperpolarization of postsynaptic neuron further from threshold http://www.blackwellscience.com/matthews/neurotrans.htm l

27. Synaptic Integration Multiple synaptic events have an additive effect on membrane potential –summation Sum of inputs determines whether axon hillock depolarized enough for AP to form.

28. Spatial Summation numerous presynaptic fibers may converge on a single postsynaptic neuron additive effects of numerous neurons inducing EPSPs and IPSPs on the postsyn. neuron

29. Temporal Summation additive effects of EPSPs and IPSPs occurring in rapid succession next synaptic event occurs before membrane recovers from previous event stimulus threshold membrane potential Low Frequency Stimulation High Frequency Stimulation