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

CARLOS A. PRETELL ANNAN; NICOLAS M FULGINITI; DIEGO E. PAFUNDO; BELFORTE, JUAN E

Villa Carlos Paz, Cordoba

Congreso; XXXIV Reunión anual SAN; 2019

Sociedad argentina de investigacion en neurociencias

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