Activity dependent excitatory/inhibitory imbalance in the medial prefrontal cortex pyramidal neuron inputs in a parvalbumin positive neuron dysfunction mouse model.

JUAN E. BELFORTE; CARLOS A. PRETELL ANNAN; DIEGO E. PAFUNDO

Villa Carlos Paz, Cordoba

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

Sociedad argentina de investigacion en neurociencias

In the medial Prefrontal Cortex (mPFC), cognitive processes require a balanced interplay of interneurons and pyramidal neurons (PN). In particular parvalbumin interneurons (PV) seem to be required for the balance of excitatory and inhibitory (E/I) inputs that produce membrane potential subthreshold oscillations. Importantly neurodevelopmental illnesses like schizophrenia, show dysfunction in the PV activity that may alter the PN physiology and the E/I balance. Here we focused on the effects of PV dysfunction on the membrane properties, morphology and E/I balance of PNs in the mPFC using a mouse line where the NMDAR is eliminated from corticolimbical PV neurons early on, showing molecular and behavioral markers resembling schizophrenia. Firstly, we found a reduced and less complex dendritic tree and an increased excitability in PNs of KO mice. Furthermore whereas the E/I balance was not altered in the spontaneous activity of acute slices, the miniature events displayed a reduced IPSC and normal EPSC frequencies, increasing the E/I balance. And finally, whole cell voltage clamp recordings under higher activity levels in the prefrontal cortex, as found during in vivo experiments, show an altered E/I balance in the KO mice. These results indicate that circuit alterations during early neurodevelopment imprint an altered functional connectivity that may be compensated only under low levels of circuit activity reducing the dynamic range of E/I balance control.