Cell Bio 2 Exam 2 L23: Neural Plasticity 2

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  1. What are the four stages of synaptic plasticity?
    1. Induction: a postsynaptic neuron realizes that a particular input needs to be changed

    2. Selectivity: a particular type of change is selected based upon input parameters

    3. Expression: The synaptic efficacy is changed

    4. Maintenance: This efficacy is maintained over a long period of time
  2. Modulation (Expression) of Plasticity is ____. 
    What are the types of change?
    Modulation is when synaptic efficacy is changed (time scale of minutes to hours)

    • Types: 
    • -biochemical: modulation of receptors
    • -stoichiometric: adjustment of PSD components
    • -structural: spine morphology
  3. Biochemical Modulation
    changes occur in:
    • the conductive properties of receptors
    • ligand gating
  4. Biochemical Modulation

    AMPAR phosphorylation
    • -remember CaMKII
    • -increase conductivity
  5. Biochemical Modulation

    K+ channel phosphorylation
    -ERKII mediated (similar to CamKII)

    • -decrease conductivity
    •         -K+ is concentrated inside the cell
    •         -K+ channel opening allows repolarization (because K+ leaves)
    •         -recovery of resting potential
  6. Stoichiometric Modulation 

    What is stoichiometry?
    stoichiometry: relative amount of reactants to products; i.e. amount of receptor to signaling proteins at the PSD (think of the PSD as a tiny reaction chamber)
  7. Stoichiometric Modulation
    NMDAR/AMPAR relationship
    • AMPAR is "louder" than NMDAR
    • -easier to excite
    • -stays open longer

    • NMDAR is activated first
    • -calcium influx affects the PSD-95 binding

    • AMPAR is recruited for potentiation
    • -other proteins bind PSD-95
    • -AMPAR is recruited to the PSD
  8. Stoichiometric Modulation - How does it change?

    The PSD as a location-dependent reaction chamber
    • extrasynaptic locations
    • -spine membrane versus the presynaptic terminal 
    • -diffusion and neurotransmitter uptake
    • -synaptic vesicle release
  9. Stoichiometric Modulation - How does it change?

    • little effect at extrasynaptic locations
    • PSD-95 mediates recruitment
    • synaptic AMPAR increases synaptic efficacy
  10. Structural Modulation
    • Spine morphology changes
    • -intitially: "stubby" spine
    • -potentiated: "mushroom" spine

    • What are the effects?
    • -the spine "neck" constricts (dendrite access)
    • -resistance to ionic movement = (1/cross sectional area)
    • -ohms law: V = IR; increase R = increased V, shrinking neck increases R therefore increases V
    • -increasing V helps reach threshold for action potential
  11. Maintenance of Plasticity: How are changes maintained?
    1. Molecular switches: the state of a molecule / complex is maintained

    2. bistable feedback of signaling cascades: signaling cascade turns "on"/"off" with large perturbations 

    3. Membrane trafficking: if located in the membrane, it will keep replenishing

    4. Local protein synthesis: "tagged" spines get more protein synthesized

    5. Recurrent network dynamics: cycling signals keep connections strong
  12. Maintenance: Molecular Switches
    molecular activation can occur via phosphorylation or protein binding into complexes

    • maintenance of phosporylation state:
    • -phosphorylation activates proteins
    • -some proteins can phosphorylate themselves
    • -CaMKII activation allows autophosphorylation

    • Maintenance of protein binding complexes:
    • -when partners bind, they may activate/inactive
    • -calcium/calmodulin binds CaMKII and activates it
    •        -once bound, this complex can be very stable
    •        -activated CaMKII is more likely to bind calmodulin (higher affinity)
  13. Maintenance: Bistable Signaling Networks
    A signaling network is a series of coupled proteins; a signal travels from one protein to the next and activity "jumps" between proteins in the pathway.

    • ERKII/PKC pathway: 
    • -small activations of ERKII die out along the pathway
    • -large activations of ERKII are perpetuated and result in a positive feedback loop
    • -activated ERKII activates PKC and phosporylates K+ channels
    • -positive feedback loop maintains ERKII activation and maintains K+ channel phosphorylation
  14. Maintenance: Membrane Trafficking
    • stoichiometry changes during facilitation/depression
    • -cellular machinery can replace old proteins with new
    • -if the protein is already in the PSD, the machinery replaces it there

    • Back to the NMDAR/AMPAR relationship
    • -facilitation is caused by some excitatory signals
    •          * NMDAR mediates the initial event
    •          * AMPAR increases in abundance at the PSD
    •          * AMPAR is stabilized there
    • -cellular machinery
    •          * normally replenishes AMPAR (and others)
    •          * When AMPAR is not at the PSD there is no reason for the machines to insert it
    •          * When AMPAR is abundant at the PSD the machinery inserts it there to replace the old
  15. Maintenance: Local Protein Synthesis
    • Flow of information
    • -DNA-->RNA-->protein

    • Translational regulation
    • -synthesis
    •        *activation states of proteins can affect mRNA binding and translation
    • -accesibility
    •        * if the mRNA is not around, it cannot be translated to protein
    • -"tagged"synapses
    •        * events may cause biochemical changes at the synapse; these changes can affect local protein synthesis
    •        * the type of regulation depends on plasticity; LTP may result in increased protein synthesis but LTD may result in degradation of those mRNA molecules
    •        * regulation also depends on the protein; LTP may increase synthesis of certain proteins (AMPAR) and degrade others (K+ channels)
  16. Maintenance: Recurrent Network Dynamics
    • Neuronal communication can be:
    • -point to point: info passed to different regions of the system
    • -resonant: activity can bounce back and forth between two regions
    • -cyclic: activity can circle within a region or around multiple regions

    • The pre-frontal cortex and short-term memory:
    • -pre-frontal cortex (PFC) is associated with learning and memory
    • -cognitive tasks activate the PFC
    • -learning tasks cause the activity to continue
    •        *continued cycling is afforded by attention
    •        *this denotes importance (non-attentive stimuli will die out)
    •        *reinforced stimuli are brought into long term memory
    • -intraregional cyclic recurrent network activity
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Cell Bio 2 Exam 2 L23: Neural Plasticity 2
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