Los invitamos al Seminario del Instituto Ferreyra dictado por Lucas Pozzo-Miller, PhD, Department of Neurobiology School of Medicine-University of Alabama at Birmingham.
El día JUEVES 6 de septiembre de 2018 a 13 hs en el Aula del IMMF.
Resumen: The ventral hippocampus (vHIP) of Mecp2 knockout (KO) mice is hyperactive due to an excitation/inhibition (E/I) imbalance of synaptic activity. In contrast, several cortical regions are hypoactive in Mecp2 KO mice. CA1 pyramidal neurons of the vHIP protect their axons to the medial prefrontal cortex (mPFC), forming glutamatergic synapses onto excitatory pyramidal neurons and inhibitory GABAergic interneurons. Because altering the E/I balance in the mPFC causes impairments in social behaviors that are reminiscent of autism spectrum disorders, I will present experiments that test whether vHIP hyperactivity propagates to and alters mPFC function in Mecp2 KO mice. Electrical stimulation of identified vHIP fibers evoked voltage-sensitive dye signals with larger amplitude and spatial spread in Mecp2 KO slices, while selective optogenetic stimulation of vHIP afferents evoked larger excitatory postsynaptic currents in layer 5 mPFC pyramidal neurons. Furthermore, selective chemogenetic excitation of vHIP neurons projecting to the mPFC caused deficits of social memory in WT mice that are similar to those observed in Mecp2 KO mice, while chemogenetic silencing of those same neurons improves social memory in Mecp2 KO mice. We conclude that hyperactive hippocampal afferents alter network activity in the mPFC of Mecp2 KO mice by affecting the E/I balance within the mPFC circuit, which leads to impaired social memory.