PSD-95 regulates synaptic transmission and plasticity in rat cerebral cortex

Area of Science:

• Neuroscience
• Molecular Biology
• Synaptic Plasticity

Background:

• Postsynaptic density-95 (PSD-95) is abundant in excitatory synapses, but its precise role in synaptic transmission and plasticity is unclear.
• Understanding PSD-95's function is crucial for deciphering synaptic mechanisms.

Purpose of the Study:

• To investigate the functional role of PSD-95 in regulating synaptic transmission and plasticity.
• To determine the effects of PSD-95 overexpression on excitatory synaptic currents and long-term depression.

Main Methods:

• Overexpression of PSD-95 in cortical pyramidal neurons using particle-mediated gene transfer in organotypic brain slices.
• Electrophysiological recordings to assess AMPA receptor/NMDA receptor (AMPAR/NMDAR) ratios, evoked EPSCs, and miniature EPSCs (mEPSCs).
• Paired-pulse ratio analysis to evaluate presynaptic release probability.

Main Results:

• PSD-95 overexpression increased the AMPAR/NMDAR ratio and the amplitude of evoked EPSCs.
• Increased frequency of AMPAR-mediated mEPSCs, suggesting more synapses express AMPARs.
• No change in current-voltage rectification or presynaptic release probability was observed.
• PSD-95 transfection significantly enhanced the probability of inducing long-term depression.

Conclusions:

• PSD-95 overexpression potentiates AMPA receptor-mediated synaptic transmission, likely by increasing the number of synapses expressing AMPARs.
• PSD-95 plays a critical role in controlling synaptic strength.
• PSD-95 significantly influences activity-dependent synaptic plasticity, particularly long-term depression.