-Lower density of perisomatic GABAergic boutons containing α1 subunit and Excitation/Inhibition imbalance in a mouse model of schizophrenia

FULGINITI N; PRETELL ANNAN, CARLOS A; BELFORTE JE; PAFUNDO, DIEGO ESTEBAN

Congreso; Reunion Anual de la Sociedad Argentina de Investigación en Neurociencias (SAN); 2019

Sociedad Argentina de Investigación en Neurociencias (SAN)

Schizophrenia in characterized by cognitive symptoms that are present before the onset of psychosis. Cognitiveprocesses correlate with synchronous activity, which at the neuronal level is represented by membranepotential oscillations, critical for neuron firing and produced by excitatory and inhibitory inputs. Importantly theexcitation (E) is balanced by inhibition (I), i.e. when E increases, I proportionally increases and is maintained ineach cycle in a wide range of synaptic conductance. Parvalbumin interneuron (PVI) activity seems crucial for theE/I balance, and also, PV dysfunction may lead to cognitive deficits. Thus, PVI function deficits may produce anew E/I steady state or an altered dynamic range of E/I balance, and thus alter the circuit function. We used amodel of PVI dysfunction by selectively ablating the NMDAR in corticolimbic PVIs to test if the E/I balance in theadult mPFC is altered by a PV dysfunction early. The results show that KO mice show altered E/I balance at thefunctional connectivity level that can be compensated only under low network activity. Here we propose to finda structural correlate to the E/I changes in the KO mice by estimating the GABA synapses in the mPFC.We foundthat mPFC neurons of KO mice have less α1 subunit perisomatic GABA synapses, whereas there is no change inthose containing the α2 subunit or PV. Finally, we found differences in the frequency of I inputs vs the numberof perisomatic α1 GABAergic synapses correlation.