UCSF

Adaptation to novel environments involves two classes of motivated behaviors; promoting actions that lead to positive outcomes and suppressing actions that do not lead to positive outcomes. For animals like mammals, it is likely that in any given situation many more behaviors are inhibited than are promoted. Importantly, diminished inhibitory control is a feature of many pathological conditions and maladaptive behaviors, including impulsivity.

Aspects of motivated behaviors, particularly those involving suppression of responses, in this thesis, are characterized in rodents using the DS task. In this task, presentation of a discriminative stimulus (DS) signals availability of sucrose reward upon a lever press. Importantly, presses outside the DS or during the neutral stimulus (NS) is not rewarded and is shown to be suppressed during training. Given the hypothesized role of Nucleus Accumbens (NAc) in guiding motivated behaviors, I first tested its influence on this cued appetitive task. Pharmacological inactivations of NAc differentiated a sub-region specific contribution to the DS task: NAc core promoted responding to rewarded cues while NAc shell suppressed unrewarded responding, including NS responding. Surprisingly subsequent electrophysiological recordings in NAc, only showed moderate quantitative differences between the two NAc subregions. These results, therefore, indicate that the dissociable roles of NAc subregions are attributable at least partly to their distinct projection targets.

A growing body of evidence implicates the ventromedial prefrontal cortex (vmPFC) in suppression of unnecessary actions. Since vmPFC projects heavily to NAc shell, I hypothesized that this corticostriatal projection mediates the learned inhibitory control in the DS task. Simultaneous vmPFC inactivations and NAc shell recording confirmed this hypothesis. vmPFC inactivation led to a response disinhibition with temporal patterns matching that of NAc shell inactivations. Importantly electrophysiological results indicate that vmPFC mediates its effect by controlling a dual neural mechanism in NAc shell: suppression of NS excitations which can drive behavioral responding to NS and increased firing of gating neurons that are believed to inhibit spontaneous unreinforced responding.

Together the novel results presented, help reveal the ventral corticostriatal mechanism of action suppression with important ramifications for the study of decision making and its aberrations such as impulsivity or addiction.