Synaptic Plasticity: Advanced Mechanisms

NMDA Receptor Mechanics

• Mg2+ Block Requirements:
  • Presynaptic glutamate release
  • Postsynaptic depolarization
• Ca2+ Influx Effects:
  • Activates CaMKII
  • Phosphorylates CREB
  • Triggers immediate early gene expression

Signaling Cascades in LTP

• CaMKII Activation:
  • Autophosphorylates at Thr286
  • Translocates to postsynaptic density
  • Phosphorylates AMPA receptors
• PKA Pathway Activation:
  • Elevates cAMP
  • CREB-mediated transcription
  • Synthesizes plasticity-related proteins

Structural Modifications

• Actin Cytoskeleton Remodeling:
  • F-actin polymerization
  • Spine enlargement
  • Changes in PSD-95 scaffolding
• Local Protein Synthesis:
  • Dendritic mRNA trafficking
  • Regulation of translation
  • Setting of synaptic tags

Retrograde Signaling

• Endocannabinoid System:
  • Synthesis of 2-AG and release
  • Activation of CB1 receptors
  • Modifies presynaptic activity
• Nitric Oxide Signaling:
  • Activates NO synthase
  • Diffusion affects presynaptic terminal
  • Modulates cGMP pathway

Metaplasticity

• Future plasticity influenced by past synaptic activity
• Sliding Threshold Mechanism:
  • Involves BCM theory
  • Homeostatic regulation
  • Activity-dependent switches

Compartmentalization

• Dendritic Computation:
  • Local calcium signaling effects
  • Branch-specific plasticity
  • Spatial input clustering
• Synaptic Tagging and Capture:
  • Protein synthesis-dependent phase
  • Local targeting of proteins
  • Cross-tagging phenomena

Temporal Dynamics

• Spike-Timing-Dependent Plasticity (STDP):
  • Operates with millisecond precision
  • Has critical windows
  • Involves calcium dynamics
• Homeostatic Scaling:
  • Adjusts global synaptic strength
  • Maintains activity set points
  • Compensatory mechanisms in play

This summary delves into the molecular and cellular mechanisms driving synaptic plasticity at an advanced level.