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Biology subjects

Gremel, C. M.

Publications and source records attributed to Gremel, C. M..

4 recordsLinked to original sources

Orbitofrontal cortex populations are differentially recruited to support actions

The ability to use information from ones prior actions is necessary for decision-making. While Orbitofrontal cortex (OFC) has been hypothesized as key for inferences made using cue and value-related information, whether OFC populations contribute to the use of information from volitional actions to guide behavior is not clear. Here, we used a self-paced lever-press hold down task in which mice infer prior lever press durations to guide subsequent action performance. We show that activity of genetically identified lateral OFC subpopulations differentially instantiate current and prior action information during ongoing action execution. Transient state-dependent lOFC circuit disruptions of specified subpopulations reduced the encoding of ongoing press durations but did not disrupt the use of prior action information to guide future action performance. In contrast, a chronic functional loss of lOFC circuit activity resulted in increased reliance on recently executed lever press durations and impaired contingency reversal, suggesting the recruitment of compensatory mechanisms that resulted in repetitive action control. Our results identify a novel role for lOFC in the integration of action information to guide adaptive behavior.

neuroscience↗

Mice are not automatons; subjective experience in premotor circuits guides behavior

Subjective experience is a powerful driver of decision-making and continuously accrues. However, most neurobiological studies constrain analyses to task-related variables and ignore how continuously and individually experienced internal, temporal, and contextual factors influence adaptive behavior during decision-making and the associated neural mechanisms. We show mice rely on learned information about recent and longer-term subjective experience of variables above and beyond prior actions and reward, including checking behavior and the passage of time, to guide self-initiated, self-paced, and self-generated actions. These experiential variables were represented in secondary motor cortex (M2) activity and its projections into dorsal medial striatum (DMS). M2 integrated this information to bias strategy-level decision-making, and DMS projections used specific aspects of this recent experience to plan upcoming actions. This suggests diverse aspects of experience drive decision-making and its neural representation, and shows premotor corticostriatal circuits are crucial for using selective aspects of experiential information to guide adaptive behavior.

neuroscience↗

Mechanism for differential recruitment of orbitostriatal transmission during outcomes and actions in alcohol dependence

Psychiatric disease often produces symptoms that have divergent effects on neural activity. For example, in drug dependence, dysfunctional value-based decision-making and compulsive-like actions have been linked to hypo- and hyper-activity of orbital frontal cortex (OFC)-basal ganglia circuits, respectively, however, the underlying mechanisms are unknown. Here we show that alcohol dependence enhanced activity in OFC terminals in dorsal striatum (OFC-DS) associated with actions, but reduced activity of the same terminals during periods of outcome retrieval, corresponding with a loss of outcome control over decision-making. Disrupted OFC-DS terminal activity was due to a dysfunction of dopamine-type 1 receptors on spiny projection neurons (D1R SPNs) that resulted in increased retrograde endocannabinoid (eCB) signaling at OFC-D1R SPN synapses reducing OFC-DS transmission. Blocking CB1 receptors restored OFC-DS activity in vivo and rescued outcome-based control over decision-making. These findings demonstrate a circuit-, synapse-, and computation specific mechanism gating OFC activity following the induction of alcohol dependence.

neuroscience↗

Alcohol Dependence Differentially Alters Orbitofrontal Cortex Representations of Inferred Decision-Making and Outcomes

Alcohol dependence results in long-lasting deficits in decision-making and behavioral control. Neurobiological investigations have identified orbitofrontal cortex (OFC) as important for value contributions to decision-making as well as action control, and alcohol dependence induces long-lasting changes to OFC function that persist into protracted withdrawal. However, it is unclear which contributing OFC computations are disrupted in alcohol dependence. Here, we combined a well-validated mouse model of alcohol dependence with in vivo extracellular recordings during an instrumental task in which lever press duration serves as the contingency, and lever pressing is sensitive to outcome devaluation. We found prior alcohol dependence did not impair use of duration contingency control but did reduce sensitivity to outcome devaluation. Further, alcohol dependence increased OFC activity associated with lever-pressing but decreased OFC activity during outcome-related epochs. Hence, alcohol dependence induces a long-lasting disruption to OFC function such that activity associated with actions is enhanced, but OFC activity in relation to outcomes is diminished. This has important implications for hypotheses regarding compulsive and habitual phenotypes observed in addiction.

neuroscience↗