INVESTIGADORES
TARAVINI Irene Rita Eloisa
artículos
Título:
Altered Corticostriatal Connectivity and Exploration-Exploitation Imbalance Emerge as Intermediate Phenotypes for a Neonatal Dopamine Dysfunction
Autor/es:
BRAZ B; GALIÑANES G; TARAVINI IR; BELFORTE J; MURER MG
Revista:
NEUROPSYCHOPHARMACOLOGY
Editorial:
NATURE PUBLISHING GROUP
Referencias:
Lugar: Londres; Año: 2015
ISSN:
0893-133X
Resumen:
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.