Role of dopamine in corticostriatal postnatal maturation and related behaviors.

BRAZ B; TARAVINI IRE; BELFORTE J; MURER MG

Córdoba

Congreso; XXVIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia.; 2013

Sociedad Argentina de Investigación en Neurociencia

Attention deficit hyperactivity disorder (ADHD) is currently perceived as aneurodevelopmental condition related to an hypodopaminergic state andcorticostriatal dysfunction. Neonatal dopamine depletion with 6-hydroxydopaminehas been proposed as an ADHD mouse model because it mimics key hallmarks ofthe human disease, including hyperactivity and clinical response topsychostimulants. We have previously reported functional alterations that mightunderlie these abnormal behaviors: higher striatal spontaneous activity, highersusceptibility to undergo long term depression and lower corticostriatalsynchronization and connectivity. We extended the analysis studying behavioralphenotypes on adulthood and morphology of striatal projection neurons. Inadulthood, lesioned mice exhibited elevated vertical activity, deficits in theaccelerating rotarod (a striatum dependent task) and lower interaction with salientstimuli and peers. In addition we used D1-TOM / D2-EGFP double transgenic miceto determine whether these functional changes have a morphological correlate inthe direct and indirect pathways. We found a reduction in length and complexity ofthe dendritic tree in both D1- and D2-expressing striatal projection neurons.Preliminary results show no differences in spine density. We propose thatdecreased dopamine levels during development causes a functional and structuralcorticostriatal disconnection which may underlie hyperactivity and reducedinterest in salient stimuli persisting into adulthood.