Disorders of the Nervous System
Author: Carlos Alfredo Pretell Annan | email: carlos.a.pretell@gmail.com
Carlos A. Pretell Annan 1°, Diego E. Pafundo 1°, Juan E. Belforte 1°
1° Grupo de Neurociencia de Sistemas, Instituto de Fisiología y Biofísica Bernardo Houssay (IFIBIO-Houssay), UBA-CONICET, Ciudad de Buenos Aires, Argentina.
Schizophrenia (SZ) is a chronic mental disorder frequently emerging between adolescence and adulthood. Although its etiology is still misunderstood, alterations of the prefrontal cortex (PFC) are considered to be pathophysiologically fundamental. Pathological modifications of the PFC microcircuit affect both excitatory pyramidal neurons (PNs) (reductions in dendritic spine density and excitatory synapses) and inhibitory GABAergic interneurons (INs) (diminished levels of GAD67 and PV). The normal wiring of cortical circuits relies on the proper postnatal maturation of GABAergic INs. The increment in inhibition during adolescence leads to the establishment of an adult excitation/inhibition (E/I) balance. Evidence of alterations in both the excitatory and the inhibitory components of the medial PFC microcircuit points towards an E/I imbalance in SZ, probably related to its neurodevelopmental aspect. We have shown that an early postnatal ablation of NMDA receptors in cortical GABAergic INs mainly PV INs from mice results in SZ-like neurochemical 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 inhibitory contacts to sparsely labeled PFC PNs. Although we did not find a reduction in spine density nor in excitatory contacts from the contralateral PFC, we found a reduction in the density of inhibitory contacts, yielding a structural E/I imbalance in the PFC.