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Updated: Oct 18, 2025

Subtype-selective Electroporation of Cortical Interneurons
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Gephyrin-Lacking PV Synapses on Neocortical Pyramidal Neurons.

Dika A Kuljis1, Kristina D Micheva2, Ajit Ray1

  • 1Center for the Neural Basis of Cognition, Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA.

International Journal of Molecular Sciences
|September 28, 2021
PubMed
Summary
This summary is machine-generated.

Gephyrin is crucial for inhibitory synapses. However, this study reveals that over a third of parvalbumin neuron synapses lack gephyrin, challenging its universal role.

Keywords:
GABAA receptorscorrelative fluorescence and electron microscopyfluorescent protein sensorsgephyrinintrabodylight microscopyoptogeneticsparvalbuminsynapsessynaptophysin

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Area of Science:

  • Neuroscience
  • Synaptic Biology
  • Cellular Neuroscience

Background:

  • Gephyrin is traditionally considered essential for inhibitory synapse organization, anchoring GABAARs.
  • 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.