Effects of cortical parvalbumin positive neuron dysfunction on the physiological properties of prefrontal cortex pyramidal neurons

PAFUNDO, DIEGO E; BELFORTE, JUAN E

Mar del Plata

Congreso; XXXII SAN annual meeting; 2017

Sociedad Argentina de Investigación en neurociencias

The underlying circuit mechanisms involved in cognition require a balanced interplay of interneurons and pyramidal neurons (PN). In the PFC, executive control and cognition correlates with gamma oscillations and with membrane potential (mp) subthreshold oscillations. Importantly parvalbumin interneurons (PV) are required for the generation of gamma oscillations and the balance of excitatory and inhibitory (E/I) inputs producing mp subthreshold oscillations. Thus a dysfunction in the PV activity may alter the PN physiology and the E/I balance. Such dysfunction is believed to be present in neurodevelopmental illnesses like schizophrenia, thus the study of PV dysfunction in PFC circuits is highly relevant for the understanding of cognition in health and disease. We focused on the effects of PV dysfunction on the morphology, membrane properties and E/I balance of PNs in mouse mPFC using a mouse line where the NMDAR is eliminated from corticolimbical PV neurons early on, showing molecular and behavioral markers resembling schizophrenia. 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.These results suggest that PV dysfunction early on, impacts the maturation of the circuit altering both functional and structural characteristics of PNs.