Skip to main content
Article
Gephyrin-Lacking PV Synapses on Neocortical Pyramidal Neurons
Biology Faculty Publications
  • Dika A. Kuljis, Sacred Heart University
  • Kristina D. Micheva, Stanford University
  • Ajit Ray, Carnegie Mellon University
  • Waja Wegner, Max Planck Institute of Experimental Medicine
  • Ryan Bowman, Carnegie Mellon University
  • Daniel V. Madison, Stanford University
  • Katrin I. Willig, Max Planck Institute of Experimental Medicine
  • Alison L. Barth, Carnegie Mellon University
Document Type
Peer-Reviewed Article
Publication Date
1-1-2021
Abstract

Gephyrin has long been thought of as a master regulator for inhibitory synapses, acting as a scaffold to organize γ-aminobutyric acid type A receptors (GABAARs) at the post-synaptic density. Accordingly, gephyrin immunostaining has been used as an indicator of inhibitory synapses; despite this, the pan-synaptic localization of gephyrin to specific classes of inhibitory synapses has not been demonstrated. Genetically encoded fibronectin intrabodies generated with mRNA display (FingRs) against gephyrin (Gephyrin.FingR) reliably label endogenous gephyrin, and can be tagged with fluorophores for comprehensive synaptic quantitation and monitoring. Here we investigated input- and target-specific localization of gephyrin at a defined class of inhibitory synapse, using Gephyrin.FingR proteins tagged with EGFP in brain tissue from transgenic mice. Parvalbumin-expressing (PV) neuron presynaptic boutons labeled using Cre- dependent synaptophysin-tdTomato were aligned with postsynaptic Gephyrin.FingR puncta. We discovered that more than one-third of PV boutons adjacent to neocortical pyramidal (Pyr) cell somas lack postsynaptic gephyrin labeling. This finding was confirmed using correlative fluorescence and electron microscopy. Our findings suggest some inhibitory synapses may lack gephyrin. Gephyrin-lacking synapses may play an important role in dynamically regulating cell activity under different physiological conditions.

Comments

At the time the article was written Dika Kuljis was affiliated with Center for the Neural Basis of Cognition, Department of Biological Sciences, Carnegie Mellon University.

Open access Creative Common CC BY license.

PMID: 34576197

DOI
10.3390/ijms221810032
Creative Commons License
Creative Commons Attribution 4.0 International
Citation Information

Kuljis, D. A., Micheva, K. D., Ray, A., Wegner, W., Bowman, R., Madison, D. V., Willig, K. I., & Barth, A. L. (2021). Gephyrin-lacking pv synapses on neocortical pyramidal neurons. International Journal of Molecular Sciences, 22(18), 10032. Doi.org/10.3390/ijms221810032