UCSF

Abnormal cortical circuitry and function as well as distortions in the modulatory neurological processes controlling cortical plasticity have been argued to underlie the origin of autism. Here, we chemically distorted those processes using an antidepressant drug-exposure model to generate developmental neurological distortions like those characteristics expressed in autism, and then intensively trained altered young rodents to evaluate the potential for neuroplasticity-driven renormalization. We found that young rats that were injected s.c. with the antidepressant citalopram from postnatal d 1-10 displayed impaired neuronal repetition-rate following capacity in the primary auditory cortex (A1). With a focus on recovering grossly degraded auditory system processing in this model, we showed that targeted temporal processing deficits induced by early-life antidepressant exposure within the A1 were almost completely reversed through implementation of a simple behavioral training strategy (i.e., a modified go/no-go repetition-rate discrimination task). Degraded parvalbumin inhibitory GABAergic neurons and the fast inhibitory actions that they control were also renormalized by training. Importantly, antidepressant-induced degradation of serotonergic and dopaminergic neuromodulatory systems regulating cortical neuroplasticity was sharply reversed. These findings bear important implications for neuroplasticity-based therapeutics in autistic patients.