Reciprocal Connections between Parvalbumin-Expressing Cells and Adjacent Pyramidal Cells Are Regulated by Clustered Protocadherin γ

Abstract

Functional neural circuits in the cerebral cortex are established through specific neural connections between excitatory and various inhibitory cell types. However, the molecular mechanisms underlying synaptic partner recognition remain unclear. In this study, we examined the impact of clustered protocadherin-γ (cPcdhγ) gene deletion in parvalbumin-positive (PV⁺) cells on intralaminar and translaminar neural circuits formed between PV⁺ and pyramidal (Pyr) cells in the primary visual cortex (V1) of male and female mice. First, we used whole-cell recordings and laser-scan photostimulation with caged glutamate to map excitatory inputs from layer 2/3 to layer 6. We found that cPcdhγ-deficient PV⁺ cells in layer 2/3 received normal translaminar inputs from Pyr cells through layers 2/3-6. Second, to further elucidate the effect on PV⁺-Pyr microcircuits within intralaminar layer 2/3, we conducted multiple whole-cell recordings. While the overall connection probability of PV⁺-Pyr cells remained largely unchanged, the connectivity of PV⁺-Pyr was significantly different between control and PV⁺-specific cPcdhγ-conditional knock-out (PV-cKO) mice. In control mice, the number of reciprocally connected PV⁺ cells was significantly higher than PV⁺ cells connected one way to Pyr cells, a difference that was not significant in PV-cKO mice. Interestingly, the proportion of highly reciprocally connected PV⁺ cells to Pyr cells with large unitary IPSC (uIPSC) amplitudes was reduced in PV-cKO mice. Conversely, the proportion of middle reciprocally connected PV⁺ cells to Pyr cells with large uIPSC amplitudes increased compared with control mice. This study demonstrated that cPcdhγ in PV⁺ cells modulates their reciprocity with Pyr cells in the cortex.

Keywords: clustered protocadherin; electrophysiology; excitatory-inhibitory connections; parvalbumin; reciprocal connections; visual cortex.