Disruption of NMDAR Function Prevents Normal Experience-Dependent Homeostatic Synaptic Plasticity in Mouse Primary...

Area of Science:

• Neuroscience
• Synaptic Plasticity
• Homeostatic Regulation

Background:

• Synaptic plasticity maintains neural activity within a dynamic range.
• Two models of homeostatic adaptation exist: synaptic scaling and sliding threshold (BCM theory).
• Previous research suggested synaptic scaling is NMDAR-independent, while sliding threshold is NMDAR-dependent.

Purpose of the Study:

• To investigate the role of NMDARs in experience-dependent homeostatic regulation of synaptic plasticity.
• To determine if synaptic scaling or sliding threshold model better explains observed plasticity.
• To examine NMDAR involvement in visual cortex plasticity.

Main Methods:

• Acute genetic knock-out and pharmacological block of NMDARs in mice.
• Measurement of AMPA receptor-mediated miniature EPSCs in visual cortex layer 2/3.
• Assessment of postsynaptic neuronal activity using c-Fos expression and Ca2+ imaging.

Main Results:

• NMDAR blockade prevented experience-dependent homeostatic regulation of synaptic strength.
• Both visual deprivation-induced strengthening and reinstatement-induced weakening were inhibited by NMDAR absence.
• Neuronal activity remained largely unchanged despite NMDAR inhibition.

Conclusions:

• Experience-dependent homeostatic adaptation of cortical circuits is mediated by NMDARs.
• These findings support the sliding threshold model of homeostatic plasticity.
• Sensory experience-dependent plasticity and input-specific homeostatic control in vivo require NMDAR function.