Neural Systems Plasticity and Potentiation

Neural Plasticity

change to neuronal circuitry that leads to changes in neural processing

Why is plasticity required?

store information (memory) which requires change (learning), circuit development (axons and dendrites growing), recover after injury, adaptation

Gill-withdrawl reflex in Aphysia

changes in synapses result in behavioral changes

Synaptic Plasticity

change in strength of synapse; pre-(vesicle release) or postsynaptic (receptors) or both (structural)

Intrinsic Plasticity

physiological response to EPSP/IPSPs; membrane resistance and density of ion channels

Structural Plasticity

anatomical change to alter signalling; synapse, spine, dendrite, axon morphology

Long-Term Potentiation

increased synaptic strength; more receptors

Long-Term Depression

decreased synaptic strength; less receptors

Hebbian Plasticity

neurons that fire together, wire together; cell A synapsing to cell B and helping drive firing, something is changing so cell A is more likely to drive firing of cell B (less input to get B going)

Dentate Gyrus

consists of many granule cells; main input to hippocampus

Trisynaptic Circuit of the Hippocampus

Dentate gyrus receives input from entorhinal cortex, CA3 receives input from dentate gyrus, CA1 receives input from CA3

Field Recordings

recording electrode near dendrites stem electrode forces neurons to fire action potentials, axons release glutamate which binds to AMPAR and NMDAR causing them to open and allow Na⁺ in away from electrode

Field EPSP

opposite of whole cell EPSP

Fiber Volley

electrical signal of presynaptic action potentials; positive charges flowing in

LTP Experiment

fEPSPs recorded before and after bursts of strong stimuli; fiber volley does not change; large jump in slope then stabilizes but still higher than baseline

High Frequency Stimulation (HFS)

100Hz for 1 second, repeated; effective but not physiological

Theta Bursts

patterned input with timing based on natural brain rhythms; burst if 4 pulses at 100 Hz repeated in 200 ms intervals; more physiological and efficient

LTP Synaptic Strength

presynaptic stimulation + postsynaptic depolarization repeatedly = increased strength of synapses, more likely to drive firing of postsynaptic cell

LTP Experiment Steps

collect baseline fEPSPs once every 30 seconds, average baseline, 100 Hz presynaptic stimulation (theta burst or HFS), collect fEPSPs

Input-Specificity

only synapses that are stimulated are potentiated

NMDARs in LTP

required; prolong response; coincidence detectors (need glutamate and depolarization)

Ca²⁺ in LTP

cannot occur without

LTP Pathway

NMDARs open, calcium entry, calmodulin (CaM) activated, CaMKII activated, AMPAR phosphorylated (greater conductance, more receptors, increased synaptic strength)

CaMKII

Ca/CaM-dependent protein kinase II; 12 subunits that open after binding CaM; long-lasting because of autophosphorylation

CaMKII subunit domains

association (heteromer formation), regulatory (activation, folds to block catalytic part), catalytic (acting on substrates)

CaMKII in LTP

direct phosphorylation of AMPAR and AMPAR auxiliary subunits

AMPAR Phosphorylation

increases current flowing into the synapse; bigger synaptic response

TARPs

transmembrane AMPAR regulatory proteins; anchors AMPARS to posy synaptic membrane

Silent Synapses

contain only NMDARs; unsilenced by translocation of AMPARs to synapse through LTP

Gene Expression in LTP

Ca²⁺ influx and CaMKII activates cAMP, activates CREB TF, induces gene expression, effector proteins maintain LTP

ACT-D

blocks transcription; causes loss of long lasting LTP

Animycin

blocks translation; causes loss of long lasting LTP

LTP Mainentance

formation of new and larger dendritic spines