Structural connectivity and excitation/inhibition balance in an early postnatal NMDA receptor knockout mouse model useful for the pathophysiological study of schizophrenia.

PRETELL ANNAN, CA; PAFUNDO DE; BELFORTE, JE

CABA

Congreso; XXXVII SAN Annual Congress; 2022

Sociedad Argentina de Investigación en neurociencias

Schizophrenia (SZ) is a chronic mental disorder frequently emergingbetween adolescence and adulthood. Although its etiology is still misunderstood,alterations of the prefrontal cortex (PFC) are consideredto be pathophysiologically fundamental. Pathological modifications ofthe PFC microcircuit affect both excitatory pyramidal neurons (PNs)(reductions in dendritic spine density and excitatory synapses) and inhibitoryGABAergic interneurons (INs) (diminished levels of GAD67and PV).The normal wiring of cortical circuits relies on the proper postnatalmaturation of GABAergic INs. The increment in inhibition during adolescenceleads to the establishment of an adult excitation/inhibition(E/I) balance. Evidence of alterations in both the excitatory and the inhibitorycomponents of the medial PFC microcircuit points towards anE/I imbalance in SZ, probably related to its neurodevelopmentalaspect.We have shown that an early postnatal ablation of NMDA receptors incortical GABAergic INs –mainly PV INs– from mice results in SZ-likeneurochemical and behavioral phenotypes that emerge during adulthood.However, the structural E/I balance had not been evaluated.Here we analyzed local and distal excitatory afferents and inhibitorycontacts to sparsely labeled PFC PNs. Although we did not find a reductionin spine density nor in excitatory contacts from the contralateralPFC, we found a reduction in the density of inhibitory contacts,yielding a structural E/I imbalance in the PFC.