Mechanisms of Synaptic Plasticity, Learning, and Memory

Vocabulary flashcards covering the molecular, synaptic, and structural mechanisms of learning and memory in Aplysia and the rodent hippocampus, including habituation, sensitization, LTP, LTD, and CREB-mediated plasticity.

Habituation

A form of nonassociative learning in which repeated presentation of a stimulus over and over again produces a progressively smaller behavioral response.

Sensitization

A form of nonassociative learning where exposure to a strong stimulus produces an exaggerated or intensified response to all subsequent stimuli.

Aplysia

A marine sea slug studied by Eric Kandel at Columbia University as an animal model for synaptic plasticity because of its simple nervous system, large identifiable neurons, and stereotyped circuits.

Abdominal ganglion

The region of the $Aplysia$ nervous system into which sensory information from the siphon enters and where sensory neurons synapse directly onto motor neurons.

Gill-withdrawal reflex

A defensive reflex in $Aplysia$ in which tactile stimulation of the siphon causes contraction and withdrawal of the gill muscle.

Motor neuron L7

A specific identifiable motor neuron in the $Aplysia$ abdominal ganglion that receives direct synaptic input from siphon sensory neurons and innervates the gill muscle to drive withdrawal.

Short-term depression (in habituation)

A presynaptic form of plasticity caused by the depletion of neurotransmitter vesicles available for release, leading to fewer vesicles released per action potential during repeated stimulation.

Axo-axonic synapse

A specialized synaptic arrangement in which the axon terminal of one neuron synapses directly onto the axon terminal of another neuron to modulate neurotransmitter release.

Facilitatory interneuron (L29)

A modulatory interneuron activated by tail shock that forms axo-axonic synapses onto siphon sensory neuron terminals and releases serotonin to mediate sensitization.

Protein Kinase A (PKA)

A cAMP-dependent kinase whose catalytic subunits phosphorylate presynaptic $K^+$ channels, causing channel closure, action potential prolongation, and increased $Ca^{2+}$ influx.

Ubiquitin hydrolase

A protein synthesized downstream of CREB activation during long-term sensitization that degrades the regulatory subunits of PKA, leading to persistent PKA activity in the absence of serotonin.

CREB (cAMP response element-binding protein)

A nuclear transcription factor that is phosphorylated by PKA, CaMKIV, or MAPK and binds to CRE/CaRE promoter sites to regulate gene expression required for long-term synaptic plasticity and memory.

Short-term memory

A phase of memory lasting less than $24\,\text{hours}$ that depends on post-translational modifications of pre-existing proteins rather than new gene expression.

Long-term memory

A stable phase of memory lasting greater than $24\,\text{hours}$ (days to weeks or years) that requires transcription, new protein synthesis, and structural remodeling of synapses.

NMDA receptor

An ionotropic glutamate receptor blocked by $Mg^{2+}$ at resting potentials that permits $Ca^{2+}$ entry only when postsynaptic depolarization coincides with glutamate binding.

CaMKII

A calcium/calmodulin-dependent protein kinase activated by $Ca^{2+}$ influx through NMDA receptors that phosphorylates the GluA1 subunit of AMPA receptors at Serine 831.

Serine 831 ($Ser^{831}$)

A specific site on the cytoplasmic carboxy-terminal tail of the GluA1 subunit phosphorylated by CaMKII and PKC, which enhances the single-channel conductance of the AMPA receptor.

Serine 845 ($Ser^{845}$)

A phosphorylation site on the AMPA receptor GluA1 subunit phosphorylated by PKA that enhances AMPA receptor current.

Silent synapse

An immature glutamatergic synapse that contains postsynaptic NMDA receptors but lacks functional AMPA receptors, rendering it electrically inactive at resting membrane potential until LTP induces AMPA receptor insertion.

Long-term depression (LTD)

An activity-dependent selective weakening of synaptic connections induced by low-frequency stimulation (such as $1\,\text{Hz}$ for $15\,\text{min}$) that requires NMDA receptor $Ca^{2+}$ influx and activation of protein phosphatases.

Schaffer collaterals

The axonal projection pathway from CA3 pyramidal cells that synapses onto the dendrites of CA1 pyramidal cells in the hippocampus.

Protein Phosphatase 1 (PP1)

A serine/threonine protein phosphatase whose catalytic subunit associates with regulatory targeting subunits like spinophilin in dendritic spines to dephosphorylate substrates during LTD.

PP2B (Calcineurin)

A protein phosphatase regulated by $Ca^{2+}$ bound to calmodulin that removes phosphate groups from targets to promote clathrin-mediated endocytosis of AMPA receptors during LTD.

Spinophilin

A regulatory subunit enriched in dendritic spines that binds to the catalytic subunit of Protein Phosphatase 1 (PP1).

Clathrin-mediated endocytosis (of AMPA receptors)

The internalization process by which AMPA receptors diffuse away from the postsynaptic density into the endocytic zone and enter sorting endosomes, reducing synaptic strength during LTD.

Radial arm maze

An eight-arm apparatus used to evaluate spatial learning and memory in rodents by assessing their ability to remember which arms contain food rewards.

Morris Water Maze

A spatial behavioral task in which rodents learn to swim to and locate a submerged escape platform in an open pool using distal environmental cues.

Target Quadrant (TQ)

The specific quadrant of the Morris Water Maze where the submerged escape platform was positioned during training, used during probe trials to quantify spatial memory retention.

After-hyperpolarization (AHP)

A prolonged phase of membrane hyperpolarization following an action potential burst that regulates intrinsic neuronal excitability, whose peak and slow components are reduced in aged animals overexpressing CREB.