Role of long term depression in corticostriatal postnatal maturation in vivo

BÁRBARA YAEL BRAZ, GREGORIO GALIÑANES, JUAN BELFORTE, GUSTAVO MURER

Congreso; XXVI Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia; 2011

SAN

It is assumed that neuropsychiatric disorders like obsessive-compulsive and attention deficit hyperactivity disorder stem from corticostriatal malfunction. However, the current knowledge of the functional postnatal development of these circuits and whether dopamine (DA) pathways are involved in that process is scarce. We have previously shown that early DA depletion delays the functional maturation of the corticostriatal system: striatal spontaneous activity is higher in young mice than in adult mice, but spontaneous activity remains high in adult mice that received early DA-depleting lesions (at PD2). Here we induced corticostriatal long term depression (LTD) in vivo by a saturation protocol using high frequency stimulation (HFS) of the prefrontal cortex, in young and adult mice with or without neonatal DA depleting lesion. Repeated HFS induced cumulative plastic changes. While the susceptibility to HFS is higher in young mice and adult lessioned mice than normal adults, maximal depression after repeated HFS is the same in all groups. We propose that striatal spontaneous activity reached during development determines the capacity to suffer LTD. In control adults, HFS could recruit less spontaneous active neurons so that one attempt of induction causes a lesser degree of LTD. with or without neonatal DA depleting lesion. Repeated HFS induced cumulative plastic changes. While the susceptibility to HFS is higher in young mice and adult lessioned mice than normal adults, maximal depression after repeated HFS is the same in all groups. We propose that striatal spontaneous activity reached during development determines the capacity to suffer LTD. In control adults, HFS could recruit less spontaneous active neurons so that one attempt of induction causes a lesser degree of LTD.