S-083 | Alterations in GABAAR α1 and α2 containing PVI synapses onto pyramidal neurons in the mPFC of a mouse model relevant for schizophrenia

Disorders of the Nervous System
Author: Nicolás Marcelo Fulginiti | Email: nicolasmfulginiti@gmail.com

Nicolás Marcelo Fulginiti^1°, Fernando Benítez^1°, Juan Emilio Belforte^1°,  Diego Esteban Pafundo^1°

^1° Laboratorio de Fisiología de Circuitos Neuronales, IFIBIO Houssay, UBA-CONICET, Ciudad de Buenos Aires, Argentina

Schizophrenia (SZ) is a severe neurodevelopmental illness characterized by positive and negative symptoms as well as cognitive impairment, which hinders self-sufficiency more drastically. Thus, understanding cognitive deficits is crucial for treatment. In mice, cognitive processes correlate with synchronous activity in the mPFC, maintained by reciprocal synapses between pyramidal neurons (PNs) and interneurons, particularly parvalbumin interneurons (PVIs). PVI activity seems crucial for such synchronicity and, furthermore, PVI dysfunction has been related to cognitive deficits. We employed a mouse model of PVI dysfunction, in which NMDARs are eliminated in corticolimbic interneurons, predominantly PVIs. Its phenotype displays cognitive deficits and mPFC circuit alterations, comprising excitatory/inhibitory imbalance. During development, GABAARs in PVI synapses onto the soma of PNs show a reduction of α2 and an increase in α1 subunits, which has been related to PVI synaptic maturation and has been found altered in SZ patients. We hypothesized that mPFC circuit alterations in KO mice could be related to a deficit in PVI synaptic maturation, hence we performed an immunohistochemical quantification of PN somatic puncta in the mPFC of control and KO mice, both juvenile and adult. Our preliminary results reveal differences between developmental stages and suggest a disbalanced expression of α1/α2 levels contingent to layer position in adult KO, without changes in PV puncta density.