Synaptic Molecular Architecture and Plasticity
Synapses as Molecular Machines
Core Mechanisms
Synaptic transmission depends on presynaptic vesicle cycling, postsynaptic receptor composition, scaffold proteins, adhesion molecules, and second-messenger cascades. Plasticity arises when these components are reorganized by activity, neuromodulators, and experience.
Key Molecules
Why are NMDA receptors considered coincidence detectors?
NMDA receptors require ligand binding and relief of the magnesium block by depolarization.
Correct answer: They require both glutamate binding and postsynaptic depolarization
Name one molecular process that can increase synaptic strength during plasticity.
Receptor trafficking is a canonical expression mechanism for potentiation.
Correct answer: Insertion of additional AMPA receptors into the postsynaptic membrane.
Pre- vs Postsynaptic Plasticity
Presynaptic
- Changes release probability
- Involves vesicle pools and calcium channels
Postsynaptic
- Changes receptor number or composition
- Involves scaffolds and spine morphology
Beyond Hebbian Rules
Plasticity is not limited to potentiation and depression; synapses also undergo metaplasticity, homeostatic scaling, structural remodeling, and local translation-dependent remodeling.
Open Problem
One unresolved issue is how synapse-specific molecular changes are stored and maintained amid continuous protein turnover. Another is how local translational control produces input-specific memory traces without destabilizing circuit function.
Mechanistic Dissection Strategy
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1
Step 1: Identify plasticity-inducing stimulus.
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Step 2: Measure candidate molecular changes at synapses.
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Step 3: Perturb receptors, kinases, or scaffolds.
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Step 4: Test effects on physiology and behavior.
Which protein is most directly associated with vesicle fusion machinery?
SNARE proteins mediate synaptic vesicle fusion with the presynaptic membrane.
Correct answer: SNARE