Altered Corticostriatal Connectivity and Exploration-Exploitation Imbalance Emerge as Intermediate Phenotypes for a Neonatal Dopamine Dysfunction.

BRAZ B; GALIÑANES G; TARAVINI IR; BELFORTE J; MURER MG

Mar del Plata

Congreso; XXX Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia.; 2015

Sociedad Argentina de Investigación en Neurociencia

Neonatal dopamine neuron (DAN) lesion in rodents produces hyperactivity and learning deficits and has been proposed as an attention deficit hyperactivity disorder model. However, the core cognitive and physiological intermediate phenotypes underlying this rodent syndrome remain unknown. Here we show that early DAN lesions cause deficits in exploitation of shelter, social and nutritional resources, and an imbalanced exploratory behavior, where local exploration is exacerbated and search behaviors involving sequences of goal directed actions are degraded. In vivo electrophysiological recordings and morphological reconstructions revealed an attenuation of corticostriatal (CS) functional connectivity affecting medial prefrontal inputs more markedly than cingulate and motor inputs that is accompanied by a contraction of the dendritic arbor of striatal projection neurons. Importantly, the behavioral deficits and the prefrontostriatal disconnection worsen after adolescence in DAN lesioned mice. Thus, DANs are essential during postnatal development for the functional and structural maturation of CS connections. From a bottom-up viewpoint, our findings suggest that neuropsychiatric conditions presumably linked to developmental alterations of the dopaminergic system should be evaluated for deficits in foraging and structural disorganization of the CS system.