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    Neurophysiology Neurophysiology Presentation Transcript

    • Psyc 689 Clin Psychopharmacology Neurophysiology
    • Neuron Components
      • Soma (Cell Body)
      • Neurites (any process that extends from cell body)
        • Axon
        • Dendrites
      • Terminal Buttons
      Pre Post
    • 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 )
    • Bipolar - Unipolar Neurons
    • 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)
    • 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 respect to outside
      -70 mV Chamber Axon Voltmeter Microelectrode
    • 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
    • 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
    • [Ion] Relative to Membrane
    • 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)
    • -70 mV -60 mV -70 mV -65 mV Decremental Conduction -70 mV -55 mV Pre-synaptic Neuron Post-synaptic Neuron
    • 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
    • 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.
    • 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)
    • 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
    • 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
    • Saltatory Conduction
    • 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
    • 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
    • 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
    • Figure 4-18b, Sherwood, 2001
    • Can be bi-directional Transmission Direction No Transmission Delay Ionic current Transmitter Gap-junction channel Structural Unit(s) Yes Cytoplasmic continuity? 3.5 nm Distance between Membranes Electrical Synapse Property Unidirectional Yes (usually 1-5 msec) Chemical transmitter (can be modified using drugs) Many (vesicles, docking/fusion proteins, and postsynaptic receptors) No 20-40 nm Chemical Synapse
    • Receptor’s View of the Presynaptic Terminal Figure 5.11, Bear, 2001 Before stimulation (and 10msec after stimulation) 1msec after stimulation
    • 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
    • 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 )
    • 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
    • G Protein-Coupled Receptors
    • 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
    • EPSP Generation (NA + Influx) The equil point for NA is about +40 mV
    • IPSP Generation (Cl - Influx) The equil point for Cl is about –60 mV
    • 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
    • Membrane Transporters
      • Two types of transporters:
      • Membrane transporters
        • Move NT into cytoplasm
        • Reuptake blockade will increase synaptic [NT]
      • Vesicular transporters
        • Move NT into vesicles
    • 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
    • EPSP Summation Spatial Summation Temporal Summation
    • 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-