Synaptic Plasticity Notes

Basic Definition

• Ability of synapses to strengthen or weaken over time
• Fundamental mechanism for learning and memory
• Responds to patterns of activity and experience
• Both structural and functional changes occur

Types of Synaptic Plasticity

1. Long-Term Potentiation (LTP):

   • Persistent strengthening of synapses
   • Requires NMDA receptor activation
   • Calcium influx triggers cascades
   • AMPA receptor trafficking increases
   • Key Features:
     • Input specificity
     • Cooperativity
     • Associativity

2. Long-Term Depression (LTD):

   • Sustained decrease in synaptic strength
   • Often involves NMDA receptors
   • Lower calcium influx than LTP
   • AMPA receptor endocytosis
   • Important for synaptic refinement

Molecular Mechanisms

Early Phase:

• Calcium entry through NMDA receptors
• CaMKII activation
• AMPA receptor phosphorylation
• Increased receptor conductance
• Receptor trafficking to membrane

Late Phase:

• Protein synthesis required
• Gene transcription changes
• New dendritic spine formation
• Structural modifications
• CREB pathway activation

Synaptic Scaling

• Homeostatic plasticity mechanism
• Maintains overall network stability
• Adjusts all synapses proportionally
• Prevents runaway excitation/inhibition

Spike Timing-Dependent Plasticity

• Depends on precise timing of pre/post spikes
• Critical window (~20ms)
• Earlier activation strengthens connection
• Later activation weakens connection

Role in Learning

Memory Formation:

• Initial encoding through early LTP
• Consolidation requires late LTP
• Synaptic tagging and capture
• Systems consolidation

Memory Maintenance:

• Structural changes
• Protein synthesis
• Epigenetic modifications
• Synaptic competition

Clinical Relevance

• Alzheimer's disease
• Schizophrenia
• Autism spectrum disorders
• Depression
• Learning disabilities

Factors Affecting Plasticity

• Age
• Stress
• Sleep
• Exercise
• Diet
• Neurotransmitter balance
• Hormones

Research Methods

• Electrophysiology
• Calcium imaging
• Electron microscopy
• Optogenetics
• Molecular biology techniques

Future Directions

• Therapeutic targeting
• Neural interface development
• Artificial synaptic devices
• Understanding metaplasticity
• Mapping plasticity rules

This biological mechanism remains central to our understanding of learning, memory, and neural adaptation.