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Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
Neurophysiology
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Neurophysiology

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  • 1. Psyc 689 Clin Psychopharmacology Neurophysiology
  • 2. Neuron Components Soma (Cell Body) Neurites (any process that extends from cell body) Axon Dendrites Terminal Buttons Pre Post
  • 3. Classification of Neurons Number of axon processes (unipolar, bipolar, multipolar) Number of dendritic processes Function Sensory, motor, interneurons Neurotransmitter (NT) used by neuron (e.g. cholinergic neurons) Effects of NT (excitatory vs. inhibitory)
  • 4. Bipolar - Unipolar Neurons
  • 5. Neuron Cell Structure Cell Specializations: Support, contraction, conduction, secretion Nerve cells are specialized for communication (nerves conduct ELECTROCHEMICAL signals) Cell components Membrane: bilipid layer contains ion channels and receptors Cytoplasm Mitochondria (energy for cell) Nucleus (contains DNA, guides protein synthesis) Microfilaments and tubules: transport functions Transporters (membrane, vesicular)
  • 6. Measuring Nerve Cell Resting Membrane Potential Giant squid axon is placed in seawater in recording chamber Glass microelectrode is inserted into axon Voltage measures -70 mV inside with -70 mV Chamber Axon Voltmeter Microelectrode
  • 7. Resting Membrane Potential RMP is a balance point between Concentration gradients Electrical gradients RMP reflects a selective permeability to K+ At rest, some K+ can leave cell, causing the exterior of the nerve cell membrane to be slightly positive relative to the inside of the axon RMP can change briefly (local potentials) Depolarizing Hyperpolarizing
  • 8. Ion Channels Channels allow for entry/efflux of ions Channel opening/closing mechanisms: Ligand-gated Second messenger-gated Voltage-gated Stretch-gated Impact of ion channel will depend on charge/direction of ion flow
  • 9. [Ion] Relative to Membrane ION: [OUT] [IN] ====================================== NA+ 120 10 K+ 3 140 CL- 120 3 AN- NIL 100 ========================================
  • 10. Local Potentials Local disturbances of membrane potential are carried along the membrane : Local potentials degrade with time and distance Local potentials can summate to produce an action potential (AP)
  • 11. -70 mV -60 mV -70 mV -65 mV Decremental Conduction -70 mV-55 mV Pre-synaptic Neuron Post-synaptic Neuron
  • 12. Axon Action Potentials are generated in the initial segment (axon hillock) when the RMP rises above threshold. The initial segment has a high density of voltage-gated sodium channels. PSP’s PSP’s PSP’s
  • 13. The Action Potential (AP) An AP is a stereotyped change in membrane potential If RMP moves past threshold, membrane potential quickly moves to +40 mV and then returns to resting level (-70 mV) Ionic basis of the AP: NA+ in: upswing of spike Diffusion, electrostatic pressure K+ out: downswing of spike Source: Fig 4.14 from Kolb, Whishaw (2001) Brain and Behavior.
  • 14. Action Potential Properties The action potential: Is an “all or none” event: RMP either passes threshold or doesn’t Is propagated down the axon membrane Notion of “successive patches” of membrane Has a fixed amplitude: AP’s don’t signal information via a change in height APs vary in frequency to signal information Has a conduction velocity (10-100 meters/sec) Has a refractory period in which stimulation will not produce an AP (limits the firing rate)
  • 15. Membrane Refractory Periods Absolute: ~1 msec (during impulse) Relative: following repolarization RP’s limit the firing rate of nerve cells 1 msec RP would = 1000 pulses per second Absolute RP explains why AP typically cannot travel in 2 directions simultaneously
  • 16. Saltatory Conduction AP’s are propagated down axon AP depolarizes each successive patch of membrane Slows down transmission in nonmyelinated axons Myelinated axons: AP jumps from node to node: only depolarizes membrane at node Saltatory conduction speeds up velocity and allows for smaller diameter axons
  • 17. Saltatory Conduction
  • 18. Inter-Neuron Signaling Messages from one nerve cell are passed onto another nerve cell: Direct electrical contact Chemical signals between neurons? Nerve cells release chemicals: The Loewi study
  • 19. Synapses The “synapse” is the physical gap between pre- and post-synaptic membranes (~20-40 nMeters) Presynaptic membrane is typically an axon The axon terminal contains Mitochondria that provide energy for axon functions Vesicles (round objects) - contain neurotransmitter molecules Cisternae (part of the Golgi apparatus): recycle vesicles Postsynaptic membrane can be A dendrite (axodendritic synapse) A cell body (axosomatic synapse) Another axon (axoaxonic synapse) Postsynaptic thickening lies under the axon terminal and contains receptors for transmitters
  • 20. Types of Synapses • Electrical • Chemical •Found in: escape reflex neurons (e.g. goldfish) •Epithelial cells (gut) •Cardiac muscle cells (heart) •Found in: Almost all mammalian neurons Figure 5.1a, Bear, 2001 Figure 5.10, Bear, 2001
  • 21. Figure 4-18b, Sherwood, 2001
  • 22. Property Electrical Synapse Distance between Membranes 3.5 nm Cytoplasmic continuity? Yes Structural Unit(s) Gap-junction channel Transmitter Ionic current Transmission Delay No Transmission Direction Can be bi- directional Chemical Synapse 20-40 nm No Many (vesicles, docking/fusion proteins, and postsynaptic receptors) Chemical transmitter (can be modified using drugs) Yes (usually 1-5 msec) Unidirectional
  • 23. Receptor’s View of the Presynaptic Terminal Figure 5.11, Bear, 2001 Before stimulation (and 10msec after stimulation) 1msec after stimulation
  • 24. Neurotransmitter Release Vesicles lie “docked” near the presynaptic membrane The arrival of an action potential at the axon terminal opens voltage-dependent CA++ channels CA++ ions flow into the axon CA++ ions change the structure of the proteins that bind the vesicles to the presynaptic membrane A fusion pore is opened, which results in the merging of the vesicular and presynaptic membranes The vesicles release their contents into the synapse Released transmitter then diffuses across cleft to interact with postsynaptic membrane receptors
  • 25. Postsynaptic Receptors Molecules of neurotransmitter (NT) bind to receptors located on the postsynaptic membrane Receptor activation opens postsynaptic ion channels Ions flow through the membrane, producing either depolarization or hyperpolarization The resulting postsynaptic potential (PSP) depends on which ion channel(s) open Postsynaptic receptors alter ion channels Directly (ionotropic receptors) Indirectly, using second messenger systems that require energy (metabotropic receptors)
  • 26. Ligand-gated Ion Channel Receptors Note that Cl- is responsible for hyperpolarization Note that Na+ is responsible for depolarization These receptors are made up of 5 subunits each with 4 TM segments
  • 27. G Protein-Coupled Receptors
  • 28. Postsynaptic Potentials PSPs are either excitatory (EPSP) or inhibitory (IPSP) Opening NA+ ion channels results in an EPSP Opening K+ ion channels results in an IPSP Opening Cl- ion channels results in an IPSP Depends on value of membrane potential PSPs sweep along the membrane Degrade with distance and time Length and time constants
  • 29. EPSP Generation (NA+ Influx) The equil point for NA is about +40 mV
  • 30. IPSP Generation (Cl- Influx) The equil point for Cl is about –60 mV
  • 31. Termination of Postsynaptic Potentials NT binding to a postsynaptic receptor results in a temporary PSP Termination of PSPs is accomplished via Reuptake: the NT molecule is transported back into the cytoplasm of the presynaptic membrane The NT molecule can be reused Vesicular transporters can move NT into vesicles Enzymatic deactivation: an enzyme destroys the NT molecule Diffusion away from the receptor sites
  • 32. Membrane Transporters Two types of transporters: Membrane transporters Move NT into cytoplasm Reuptake blockade will increase synaptic [NT] Vesicular transporters Move NT into vesicles
  • 33. Synaptic Integration PSPs sweep along the dendritic membrane The amplitude of a PSP varies with time and distance Length constant: larger values mean greater amplitude over a fixed distance Neural integration involves the algebraic summation of PSPs A predominance of EPSPs at the axon hillock can result in an action potential If the summated PSPs do not drive the axon membrane past threshold, no action potential will occur
  • 34. EPSP Summation Spatial Summation Temporal Summation
  • 35. Property Action Pot EPSP IPSP Direction More + Depolarization More + Hypopolarization More - Hyperpolarization Magnitude All or None -70 to threshold -70 to -96 -70 to +30 Conduction Properties Decremental Decremental Decremental Duration 2-3 msec 15-20 msec 15-20 msec Non-

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