Gephyrin-Lacking PV Synapses on Neocortical Pyramidal Neurons

Area of Science:

• Neuroscience
• Synaptic Biology
• Cellular Neuroscience

Background:

• Gephyrin is traditionally considered essential for inhibitory synapse organization, anchoring GABA_ARs.
• Gephyrin immunostaining is widely used as a marker for inhibitory synapses.
• The precise localization of gephyrin across all inhibitory synapse types remains incompletely understood.

Purpose of the Study:

• To investigate the input- and target-specific localization of gephyrin at defined inhibitory synapses.
• To determine if gephyrin is present at all inhibitory synapses formed by specific neuronal populations.

Main Methods:

• Utilized genetically encoded fibronectin intrabodies (FingRs) against gephyrin, tagged with EGFP, in transgenic mice.
• Labeled presynaptic parvalbumin (PV) neuron boutons using Cre-dependent synaptophysin-tdTomato.
• Employed correlative fluorescence and electron microscopy for high-resolution analysis.

Main Results:

• Demonstrated reliable labeling of endogenous gephyrin using Gephyrin.FingR.
• Found that over one-third of PV neuron presynaptic boutons adjacent to neocortical pyramidal cell somas lacked postsynaptic gephyrin.
• Confirmed the absence of gephyrin at a significant proportion of inhibitory synapses.

Conclusions:

• Challenges the notion that gephyrin is universally present at all inhibitory synapses.
• Suggests the existence of gephyrin-lacking inhibitory synapses.
• Proposes that gephyrin-lacking synapses may play a role in dynamic neural activity regulation.