The ability to inhibit a behavior has been widely shown to be impaired across development. Furthermore, the adolescent period coincides with a heightened rate of diagnosis for a number of neurodevelopmental disorders such as ADHD and schizophrenia, as well as increased prevalence of drug abuse and addiction, all of which are characterized by deficits in inhibitory behavior. However, both the behavioral and neurobiological nature of these impairments remains unclear. The proposed research will test the theory that inhibitory behavior depends on the dynamic interplay between subcortical brain systems critical to emotional and incentive-based behavior and cortical brain systems mediating cognitive and impulse control. Recent evidence suggests that a disparity between structural and functional maturity within frontostriatal circuits during adolescence contributes to the tendency towards disproportionate emotional and reward-sensitive behavior displayed during this developmental period. Of particular relevance is the nucleus accumbens (NAcc), which has been heavily implicated in reward- related learning and is functionally mature in adolescence. Conversely, the prefrontal cortex (PFC), which is essential for cognitive control, does not mature until much later in the adolescent period. Thus, Specific Aim 1 will establish the developmental timeline for the relative contributions of PFC and NAcc during inhibitory learning in adolescence. This will be accomplished by quantifying protein expression levels of the immediate early gene Arc during negative occasion setting, a form of inhibitory learning that has significant translational relevance and is well suited for the transient adolescent period. To complement these findings, Specific Aim 3 will causally test whether coordinated activation of PFC and NAcc is required for the expression of learned inhibition. If the disparity between functional maturatio of PFC and NAcc present in adolescence is responsible for the inhibition difficulties observed during this developmental period, then mimicking this disparity in adults prior to negative occasion setting training should produce a similar impairment. Together, these two aims will not only inform theories regarding basic brain-behavior development, but will also provide insights that may lead to the identification and development of new treatments for addiction and other forms of mental illness.
This project will provide valuable new insights into the neurobiological correlates and development of inhibitory behavior. Investigating the link between neurobiological and behavioral development may also inform the identification and development of new treatments for addiction and neurodevelopmental disorders such as Attention Deficit Hyperactivity Disorder and schizophrenia.
| DeAngeli, Nicole E; Miller, Sarah B; Meyer, Heidi C et al. (2017) Increased sign-tracking behavior in adolescent rats. Dev Psychobiol 59:840-847 |
| Meyer, Heidi C; Bucci, David J (2017) Negative occasion setting in juvenile rats. Behav Processes 137:33-39 |
| Meyer, Heidi C; Bucci, David J (2017) Setting the occasion for adolescent inhibitory control. Neurobiol Learn Mem 143:8-17 |
| Meyer, Heidi C; Bucci, David J (2016) Neural and behavioral mechanisms of proactive and reactive inhibition. Learn Mem 23:504-14 |
| Meyer, Heidi C; Bucci, David J (2016) Imbalanced Activity in the Orbitofrontal Cortex and Nucleus Accumbens Impairs Behavioral Inhibition. Curr Biol 26:2834-2839 |
| Meyer, Heidi C; Chodakewitz, Molly I; Bucci, David J (2016) Nicotine administration enhances negative occasion setting in adolescent rats. Behav Brain Res 302:69-72 |
| Meyer, Heidi C; Bucci, David J (2016) Age differences in appetitive Pavlovian conditioning and extinction in rats. Physiol Behav 167:354-362 |
