Seminario INGEBI

Viernes 5 de Abril 13:20 hs.

Dr. Javier Zorrilla de San Martín

Institut du Cerveau et de la Moelle Epinière

ICM Paris, France.

Cortical inhibitory circuits in Down síndrome

High level cognitive abilities such as attention, working memory and cognitive flexibility are key to carry a normal life. These functions depend on the integrity of the prefrontal cortex, which is proposed to play an important role in the integration of internally and externally generated information and coordination of brain networks, both critical for executive functions. This coordinated brain activity is reflected in neural oscillations, rhythmic fluctuations of electrical activity that strongly rely on the correct function of GABAergic inhibitory circuits.

Down syndrome is characterized by mild to severe intellectual deficits and, remarkably, have marked deficits in PFC-dependent executive functions. These deficits have been proposed to be caused by an excess of inhibition however it is not yet clear which circuits are altered, which are the cellular mechanisms nor how these alterations affect network coordination and finally behavior.

Using a mouse model of Down syndrome and fluorescent reporter lines for specific neuronal subtypes we could perform electrophysiological recordings and neuroanatomical reconstructions of specific neuronal types composing cortical inhibitory circuits. We have characterized two circuit specific mechanisms that account for excessive inhibition in the prefrontal cortex of Ts65Dn mice: one produced by synaptic enhancement of the dendritic inhibitory loop formed between pyramidal neurons and somatostatin positive interneurons and the other due to an increase in the excitability of Parvalbumin positive interneurons. These mechanisms are likely to make part of the neurobiological causes of intellectual disabilities in Down syndrome.