Neural activity alterations and functional connectivity deficits in a developmental mouse model of schizophrenia

RODRIGO J ÁLVAREZ, CAMILA L ZOLD, JUAN E BELFORTE

Congreso; XXIX Congreso Anual de la Sociedad Argentina de Neurociencias; 2014

Restricted genetic ablation of NMDA receptors in cortical parvalbumin interneurons, during early postnatal development, resulted in impaired maturation of GABAergic cell function, which was sufficient to trigger the development of schizophrenia-like phenotypes in adulthood. The medial prefrontal cortex (mPFC) has been involved in the development of schizophrenic symptoms. Normal refinement of mPFC connectivity continues up to young adulthood and includes synaptic pruning of local and distant inputs, including hippocampal ones. To elucidate the pathophysiological changes leading to schizophrenia-like phenotype in our model we focused in the status of neuronal activity and functional connectivity of mPFC. Single unitary neuronal activity was recorded using tetrodes placed in the mPFC of urethane anesthetized control and mutant mice. Local field potentials were acquired from mPFC and ventral hippocampus (vHP) to characterize global brain states and to analyze neuronal entrainment with cortical rhythms. Global analysis of all recorded units shows a significant increase in the mean firing rate in mutant mice during desynchronized state, but not during slow wave state, compared with controls. Neuronal entrainment to delta, theta, and gamma oscillations will be presented independently for each state. Our results are consistent with the notion that an hyperactive, uncoordinated cortical network, with decreased signal to noise ratio, will be subjacent to the behavioral phenotypes.