Neurophysiology

1. Neurophysiology • Human physiology background: - Neuroglia - Basic properties of the Action Potential and Graded potential - Properties of the synapses and neurotransmitters

2. Organization of the nervous system (review) • Electrical signals in neurons - review - Nernst equation • Cell-to-cell communication in the nervous system - Action potentials - Graded potentials • Integration of neural information transfer

3. Organization of the Nervous system

4. Neurons --- Glial cells

5. Organization of the nervous system (review) • Electrical signals in neurons - review - Nernst equation • Cell-to-cell communication in the nervous system • Integration of neural information transfer

7. Membrane Resting Potential RMP • If [K+]inside = 150 mM and • [K+]outside = 5 mM •  potential = -67 mV across the plasma membrane • Na+/K+ pump produces -3 mV  observed RMP = -70 mV For muscle and nerve cells: observed RMP range from about -50 to about -90 mV.

8. Organization of the nervous system (review) • Electrical signals in neurons - review - Nernst equation • Cell-to-cell communication in the nervous system - Action potentials - Graded potentials • Integration of neural information transfer

9. Electrical Signals: Nernst Equation • Predicts membrane potential for single ion • Membrane potential is influenced by • Concentration gradient of ions • Membrane permeability to those ions

11. Electrical Signals: GHK Equation • Predicts membrane potential using multiple ions (Goldman-Hodgkin-Katz equation)

12. Organization of the nervous system (review) • Electrical signals in neurons - review - Nernst equation • Cell-to-cell communication in the nervous system - Action potentials - Graded potentials • Integration of neural information transfer

13. Electrical Signals: Ion Movement • Resting membrane potential determined by • K+ concentration gradient • Cell’s resting permeability to K+, Na+, and Cl– • Gated channels control ion permeability • Mechanically gated • Chemical gated • Voltage gated • Threshold voltage varies from one channel type to another

14. Electrical Signals: Action Potentials Figure 8-9

15. Electrical Signals: Voltage-Gated Na+ Channels Na+ channels have two gates: activation and inactivation gates Figure 8-10a

16. Electrical Signals: Voltage-Gated Na+ Channels Figure 8-10c

17. Electrical Signals: Voltage-Gated Na+ Channels Figure 8-10d

18. Electrical Signals: Voltage-Gated Na+ Channels Figure 8-10a

19. Electrical Signals: Voltage-Gated Na+ Channels Figure 8-10c

20. Electrical Signals: Voltage-Gated Na+ Channels Figure 8-10d

21. Electrical Signals: Ion Movement during an Action Potential Figure 8-11

22. Electrical Signals: Refractory Period Action potentials will not fire during an absolute refractory period Figure 8-12

23. An action potential is an all-or-none phenomenon They are all identical Since we cannot increase the AP strength with the stimulus, how do we code for stimulus intensity?

24. Electrical Signals: Coding for Stimulus Intensity Figure 8-13a

25. Graded potential enters trigger zone Voltage-gated Na+ channels open and Na+ enters axon Positive charge spreads along adjacent sections of axon by local current flow Local current flow causes new section of the membrane to depolarize The refractory period prevents backward conduction; loss of K+ repolarizes the membrane Electrical Signals: Trigger Zone

26. Speed of action potential in neuron influenced by Diameter of axon Larger axons are faster Resistance of axon membrane to ion leakage out of the cell Myelinated axons are faster Electrical Signals: Speed of AP

27. Saltatory conduction Multiple sclerosis Electrical Signals: Myelinated Axons Figure 8-18b

28. Electrical Signals: Effect of extracellular potassium concentration of the excitability of neurons Figure 8-19b

29. Organization of the nervous system (review) • Electrical signals in neurons - review - Nernst equation • Cell-to-cell communication in the nervous system - Action potentials - Graded potentials • Integration of neural information transfer

30. Electrical Signals: Graded Potentials Subthreshold and suprathreshold graded potentials in a neuron Figure 8-8a

32. Organization of the nervous system (review) • Electrical signals in neurons - review - Nernst equation • Cell-to-cell communication in the nervous system - Action potentials - Graded potentials • Integration of neural information transfer

33. Organization of the nervous system • Electrical signals in neurons • Cell-to-cell communication in the nervous system • Integration of neural information transfer - Synaptic events - Neurocrines - Post-synaptic responses - Inactivation - Signal integration - Divergence – convergence - Summation (spatial and temporal) - Pre and post synaptic inhibitions - Long Term Potentiation - Cone growth

34. An action potential depolarizes the axon terminal. 1 Action potential 2 The depolarization opens voltage- gated Ca2+ channels and Ca2+ enters the cell. Axon terminal 3 Calcium entry triggers exocytosis of synaptic vesicle contents. Synaptic vesicle 4 Neurotransmitter diffuses across the synaptic cleft and binds with receptors on the postsynaptic cell. 1 3 Ca2+ 5 Neurotransmitter binding initiates a response in the postsynaptic cell. Voltage-gated Ca2+ channel Ca2+ Docking protein 2 4 Receptor 5 Postsynaptic cell Cell response Synaptic events: review Figure 8-21, steps 1–5

35. Cell-to-Cell: Neurocrines • Seven classes by structure • Acetylcholine • Amines • Amino acids • Purines • Gases • Peptides • Lipids

36. Cell-to-Cell: Acetylcholine Figure 8-22

37. Cell-to-Cell: Amine • Derived from single amino acid • Tyrosine • Dopamine • Norepinephrine is secreted by noradrenergic neurons • Epinephrine • Others • Serotonin is made from tryptophan • Histamine is made from histadine

38. Cell-to-Cell: Amino Acids • Glutamate: Excitatory  CNS • Aspartate: Excitatory  brain • GABA: Inhibitory  brain • Glycine • Inhibitory  spinal cord • May also be excitatory

39. Cell-to-Cell: Neurocrines • Peptides • Substance P and opioid peptides • Purines • AMP and ATP • Gases • NO and CO • Lipids • Eicosanoids

40. Cell-to-Cell: Receptors • Cholinergic receptors • Nicotinic on skeletal muscle, in PNS and CNS • Monovalent cation channels  Na+ and K+ • Muscarinic in CNS and PNS • Linked to G proteins • Adrenergic Receptors •  and  • Linked to G proteins

41. Presynaptic axon Glutamate 6 1 Glutamate is released. 1 2 Net Na+ entry depolarizes the postsynaptic cell. Ca2+ Na+ Mg2+ Depolarization ejects Mg2+ and opens channel. 3 3 Ca2+ enters cytoplasm. 4 AMPA receptor 2 4 NMDA receptor 5 Cell becomes more sensitive to glutamate. Na+ Ca2+ Paracrine release Paracrine from postsynaptic cell enhances glutamate release. 6 5 Postsynaptic cell Ca2+ entry activates second messenger pathways. Cell-to-Cell: Glutaminergic Receptors • Important during the learning process • The post-synaptic neuron sends signals back to the pre-synaptic neuron  induce changes in pre-synaptic neuron • The pre-synaptic signal is received by two different receptors Figure 8-30

42. Presynaptic axon Glutamate 1 Glutamate is released. 1 Postsynaptic cell Glutaminergic Receptors: Long-term potentiation Figure 8-30, step 1

43. Presynaptic axon Glutamate 1 Glutamate is released. 1 2 Net Na+ entry depolarizes the postsynaptic cell. Na+ AMPA receptor 2 Na+ Postsynaptic cell Glutaminergic Receptors: Long-term potentiation Figure 8-30, steps 1–2

44. Presynaptic axon Glutamate 1 Glutamate is released. 1 2 Net Na+ entry depolarizes the postsynaptic cell. Na+ Mg2+ 3 Depolarization ejects Mg2+ and opens channel. 3 AMPA receptor 2 NMDA receptor Na+ Postsynaptic cell Glutaminergic Receptors: Long-term potentiation Figure 8-30, steps 1–3

45. Presynaptic axon Glutamate 1 Glutamate is released. 1 2 Net Na+ entry depolarizes the postsynaptic cell. Ca2+ Na+ Mg2+ 3 Depolarization ejects Mg2+ and opens channel. 3 4 Ca2+ enters cytoplasm. AMPA receptor 2 4 NMDA receptor Na+ Ca2+ Postsynaptic cell Glutaminergic Receptors: Long-term potentiation Figure 8-30, steps 1–4

46. Presynaptic axon Glutamate 1 Glutamate is released. 1 2 Net Na+ entry depolarizes the postsynaptic cell. Ca2+ Na+ Mg2+ 3 Depolarization ejects Mg2+ and opens channel. 3 4 Ca2+ enters cytoplasm. AMPA receptor 2 4 NMDA receptor 5 Cell becomes more sensitive to glutamate. Na+ Ca2+ Paracrine release 5 Postsynaptic cell Ca2+ entry activates second messenger pathways. Glutaminergic Receptors: Long-term potentiation Figure 8-30, steps 1–5

47. Presynaptic axon Glutamate 6 1 Glutamate is released. 1 2 Net Na+ entry depolarizes the postsynaptic cell. Ca2+ Na+ Mg2+ 3 Depolarization ejects Mg2+ and opens channel. 3 4 Ca2+ enters cytoplasm. AMPA receptor 2 4 NMDA receptor 5 Cell becomes more sensitive to glutamate. Na+ Ca2+ Paracrine release Paracrine from postsynaptic cell enhances glutamate release. 6 5 Postsynaptic cell Ca2+ entry activates second messenger pathways. Glutaminergic Receptors: Long-term potentiation Figure 8-30, steps 1–6

48. Presynaptic axon terminal Slow synaptic potentials and long-term effects Rapid, short-acting fast synaptic potential Neurotransmitter G protein– coupledreceptor Chemically gated ion channel R G Inactive pathway Postsynaptic cell Alters open state of ion channels Activated second messenger pathway Modifies existing proteins or regulates synthesis of new proteins Ion channels open Ion channels close More K+ out or Cl– in More Na+ in Less K+ out Less Na+ in IPSP = inhibitory hyperpolarization EPSP = excitatory depolarization EPSP = excitatory depolarization Coordinated intracellular response Postsynaptic Response: Fast and slow responses in postsynaptic cells • Fast channel: cholinergic nicotinic channel • Slow channel: cholinergic muscarinic channel Figure 8-23

49. Inactivation of Neurotransmitters Figure 8-24 (1 of 3)

50. Integration: Convergence and Divergence Figure 8-25a