This application outlines a training plan and experimental procedures to ensure that the applicant will receive technical and intellectual development toward independence. The application focuses on neuronal bases of motivated behavior in adolescents, a topic with important implications for basic science and public health. Adolescents are particularly vulnerable to drug addiction and other psychopathological illnesses. This vulnerability may be a result of ongoing prefrontal cortex (PFC) and striatal development during adolescence. However, little is known about how neuronal activity within these brain regions during the expression of motivated behavior differs as a function of age. The applicant has developed the Cued Response Inhibition Task, or CRIT, to measure the ability to withhold a response during an inhibitory cue, then respond promptly following cue termination. Preliminary data demonstrate that adolescent rats are unable to respond as quickly as adults following cue termination, a behavioral difference that appears to be related to inability to adequately sustain attention to the cue. It is hypothesized that this behavioral profile will be associated with aberrant neuronal encoding of task events in PFC and striatal subregions in adolescent compared to adult rats. To test this hypothesis, two aims are proposed, both of which involve application of methodologies and data analysis that are novel for the applicant.
The first aim will involve recording single unit activity simultaneously from two brain regions during CRIT performance: anterior cingulate cortex (ACC) and dorsal striatum (DS), These regions were chosen because previous rodent recording studies demonstrate that ACC phasic responses correlate with sustained attention, and that neuronal encoding in the DS differs in adolescents from adults during motivated behavior. Neural activity will be analyzed during cue presentation, instrumental response, and outcome expectation/delivery, then compared between adults and adolescents. In the second aim, neuronal interactions within ACC and DS, as well as communication between ACC and DS during CRIT will be quantified. This will involve within, and between region analysis of noise correlations between unit pairs, local field potential (LFP) spectral power, and phase-locking between single unit activity and LFP. This will provide information about communication and direction of information flow between ACC and DS, and how this relates to behavior in adolescent and adult rats. Collectively, these experiments will provide novel information on how neural processing differs between adult and adolescent rats, and how these differences correlate with age related behavioral differences.
Neural Processing in Behaving Adolescent Rats Adolescents are highly vulnerability to psychiatric illnesses including drug addiction. It is increasingly important to delineate the neuronal basis of this vulnerability to facilitate the development of behavioral and neurobiological interventions. The aim of this proposal is to characterize age-related distinctions in neural activity during motivated behavior, and to examine how these differences relate to differences in cognitive/behavioral performance.
| Simon, Nicholas W; Moghaddam, Bita (2017) Methylphenidate has nonlinear dose effects on cued response inhibition in adults but not adolescents. Brain Res 1654:171-176 |
| Simon, Nicholas W; Wood, Jesse; Moghaddam, Bita (2015) Action-outcome relationships are represented differently by medial prefrontal and orbitofrontal cortex neurons during action execution. J Neurophysiol 114:3374-85 |
| Simon, Nicholas W; Moghaddam, Bita (2015) Neural processing of reward in adolescent rodents. Dev Cogn Neurosci 11:145-54 |
