title: Altered Corticostriatal Connectivity and Exploration/Exploitation Imbalance Emerge as Intermediate Phenotypes for a Neonatal Dopamine Dysfunction.
abstract: 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. However, 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 nondirected local exploration is exacerbated, whereas 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. The 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.
authors: Systems Neuroscience Group, Institute of Physiology and Biophysics, IFIBIO 'Houssay', CONICET and University of Buenos Aires School of Medicine, Buenos Aires, Argentina.
authors: Barbara Y
authors: BY
authors: Braz
authors: Systems Neuroscience Group, Institute of Physiology and Biophysics, IFIBIO 'Houssay', CONICET and University of Buenos Aires School of Medicine, Buenos Aires, Argentina.
authors: Gregorio L
authors: GL
authors: Galiñanes
authors: Experimental Parkinsonism Lab, Institute of Pharmacology, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors: Irene R E
authors: IR
authors: Taravini
authors: Systems Neuroscience Group, Institute of Physiology and Biophysics, IFIBIO 'Houssay', CONICET and University of Buenos Aires School of Medicine, Buenos Aires, Argentina.
authors: Juan E
authors: JE
authors: Belforte
authors: Systems Neuroscience Group, Institute of Physiology and Biophysics, IFIBIO 'Houssay', CONICET and University of Buenos Aires School of Medicine, Buenos Aires, Argentina.
authors: M Gustavo
authors: MG
authors: Murer
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology*; D003342:Corpus Striatum / Q000254:growth & development* / Q000473:pathology / Q000503:physiopathology*; D003712:Dendrites / Q000473:pathology / Q000502:physiology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004567:Electrodes, Implanted; D005106:Exploratory Behavior / Q000502:physiology*; D007150:Immunohistochemistry; D051379:Mice; D009043:Motor Activity / Q000502:physiology; D009434:Neural Pathways / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology; D016627:Oxidopamine; D010641:Phenotype; D012919:Social Behavior; D013037:Spatial Behavior / Q000502:physiology
chemical_list: D016627:Oxidopamine; D004298:Dopamine