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

BRAZ BY; GALIÑANES GL; TARAVINI IRE; BELFORTE J; MURER MG

NEUROPSYCHOPHARMACOLOGY

NATURE PUBLISHING GROUP

Lugar: Londres; Año: 2015 vol. 40 p. 2576 - 2587

0893-133X

Findings showing that neonatal lesions of the forebrain dopaminergic system in rodents lead to juvenile locomotor hyperactivity and learning deficits have been taken as evidence of face validity for the attention deficit hyperactivity disorder. But the core cognitive and physiological intermediate phenotypes underlying this rodent syndrome remain unknown. Here we show that early postnatal dopaminergic lesions cause long-lasting deficits in exploitation of shelter, social and nutritional resources, and an imbalanced exploratory behavior, where non-directed local exploration is exacerbated while sophisticated search behaviors involving sequences of goal directed actions are degraded. Importantly, some behavioral deficits do not diminish after adolescence but instead worsen or mutate, particularly, those related to the exploration of wide and spatially complex environments. In vivo electrophysiological recordings and morphological reconstructions of striatal medium spiny neurons reveal corticostriatal alterations associated to the behavioral phenotype. More specifically, an attenuation of corticostriatal functional connectivity affecting medial prefrontal inputs more markedly than cingulate and motor inputs is accompanied by a contraction of the dendritic arbor of striatal projection neurons in this animal model. Thus, dopaminergic neurons are essential during postnatal development for the functional and structural maturation of corticostriatal 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 decision making, alterations in the recruitment of corticostriatal circuits during foraging tasks, and structural disorganization of the frontostriatal connections.Neuropsychopharmacology accepted article preview online, 15 April 2015. doi:10.1038/npp.2015.104.