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

Area of Science:

• Neuroscience
• Molecular Biology
• Cellular Biology

Background:

• Functional neural circuits depend on precise connections between excitatory and inhibitory neurons.
• Molecular mechanisms for synaptic partner recognition between specific neuronal types remain largely unknown.
• Parvalbumin-positive (PV+) cells are key inhibitory interneurons in cortical circuits.

Purpose of the Study:

• To investigate the role of clustered protocadherin-γ (cPcdhγ) in PV+ cells for synaptic partner recognition.
• To examine the impact of cPcdhγ deletion in PV+ cells on intralaminar and translaminar neural circuits with pyramidal (Pyr) cells in the primary visual cortex (V1).
• To elucidate how cPcdhγ influences the reciprocity of PV+-Pyr microcircuits.

Main Methods:

• Whole-cell recordings and laser-scan photostimulation with caged glutamate were used to map excitatory inputs.
• Electrophysiological recordings were performed in control and PV+-specific cPcdhγ-conditional knock-out (PV-cKO) mice.
• Analysis focused on connection probability, reciprocity, and unitary inhibitory postsynaptic current (uIPSC) amplitudes between PV+ and Pyr cells.

Main Results:

• cPcdhγ deletion in PV+ cells did not affect translaminar excitatory inputs from Pyr cells.
• While overall PV+-Pyr connection probability was unchanged, the reciprocity of connections was significantly altered in PV-cKO mice.
• PV-cKO mice showed a reduced proportion of highly reciprocally connected PV+-Pyr pairs with large uIPSC amplitudes and an increased proportion of middle reciprocally connected pairs.

Conclusions:

• Clustered protocadherin-γ in PV+ cells plays a critical role in modulating the reciprocity of synaptic connections with pyramidal cells in the cortex.
• cPcdhγ influences the specific patterns of PV+-Pyr cell connectivity, potentially by affecting the strength or nature of reciprocal interactions.
• These findings contribute to understanding the molecular basis of synaptic partner selection in the establishment of functional cortical circuits.