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Article

Gephyrin-Lacking PV Synapses on Neocortical Pyramidal Neurons

1
Center for the Neural Basis of Cognition, Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA
2
Department of Molecular and Cellular Physiology, Stanford University, Palo Alto, CA 94304, USA
3
Optical Nanoscopy in Neuroscience, Center for Nanoscale Microscopy and Molecular Physiology of the Brain, University Medical Center Göttingen, 37075 Göttingen, Germany
4
Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Kiryl D. Piatkevich
Int. J. Mol. Sci. 2021, 22(18), 10032; https://doi.org/10.3390/ijms221810032
Received: 30 July 2021 / Revised: 1 September 2021 / Accepted: 7 September 2021 / Published: 17 September 2021
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. View Full-Text
Keywords: synapses; parvalbumin; gephyrin; intrabody; GABAA receptors; synaptophysin; optogenetics; fluorescent protein sensors; light microscopy; correlative fluorescence and electron microscopy synapses; parvalbumin; gephyrin; intrabody; GABAA receptors; synaptophysin; optogenetics; fluorescent protein sensors; light microscopy; correlative fluorescence and electron microscopy
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MDPI and ACS Style

Kuljis, D.A.; Micheva, K.D.; Ray, A.; Wegner, W.; Bowman, R.; Madison, D.V.; Willig, K.I.; Barth, A.L. Gephyrin-Lacking PV Synapses on Neocortical Pyramidal Neurons. Int. J. Mol. Sci. 2021, 22, 10032. https://doi.org/10.3390/ijms221810032

AMA Style

Kuljis DA, Micheva KD, Ray A, Wegner W, Bowman R, Madison DV, Willig KI, Barth AL. Gephyrin-Lacking PV Synapses on Neocortical Pyramidal Neurons. International Journal of Molecular Sciences. 2021; 22(18):10032. https://doi.org/10.3390/ijms221810032

Chicago/Turabian Style

Kuljis, Dika A., Kristina D. Micheva, Ajit Ray, Waja Wegner, Ryan Bowman, Daniel V. Madison, Katrin I. Willig, and Alison L. Barth. 2021. "Gephyrin-Lacking PV Synapses on Neocortical Pyramidal Neurons" International Journal of Molecular Sciences 22, no. 18: 10032. https://doi.org/10.3390/ijms221810032

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