Cortical control of striatal activity in a mouse model of attention deficit/hyperactivity disorder

GREGORIO L. GALIÑANES; IRENE R. E. TARAVINI; M. GUSTAVO MURER

JOURNAL OF NEUROSCIENCE

SOC NEUROSCIENCE

Lugar: United States; Año: 2009 vol. 29 p. 2496 - 2509

0270-6474

Altered corticostriatal information processing associated with early dopamine systems dysfunction may contribute to attention deficit/hyperactivity disorder (ADHD). Mice with neonatal dopamine-depleting lesions exhibit hyperactivity that wanes after puberty and isreduced by psychostimulants, reminiscent of some aspects of ADHD. To assess whether the maturation of corticostriatal functionalconnectivity is altered by early dopamine depletion, we examined preadolescent and postadolescent urethane-anesthetized mice with orwithout dopamine-depleting lesions. Specifically, we assessed (1) synchronization between striatal neuron discharges and oscillations infrontal cortex field potentials and (2) striatal neuron responses to frontal cortex stimulation. In adult control mice striatal neurons wereless spontaneously active, less responsive to cortical stimulation, and more temporally tuned to cortical rhythms than in infants. Striatalneurons from hyperlocomotor mice requiredmorecurrent to respond to cortical input and were less phase locked to ongoing oscillations,resulting in fewer neurons responding to refined cortical commands. By adulthood some electrophysiological deficits waned togetherwith hyperlocomotion, but striatal spontaneous activity remained substantially elevated. Moreover, dopamine-depleted animals showingnormal locomotor scores exhibited normal corticostriatal synchronization, suggesting that the lesion allows, but is not sufficient, forthe emergence of corticostriatal changes and hyperactivity. Although amphetamine normalized corticostriatal tuning in hyperlocomotormice, it reduced horizontal activity in dopamine-depleted animals regardless of their locomotor phenotype, suggesting that amphetaminemodified locomotion through a parallel mechanism, rather than that modified by dopamine depletion. In summary, functionalmaturation of striatal activity continues after infancy, and early dopamine depletion delays the maturation of core functional capacitiesof the corticostriatal system.