The ventral tegmental area (VTA) contains dopamine (DA) expressing neurons, which are critical for reward processing in the brain. DA neurons are tightly regulated by inhibitory GABA-expressing neurons; these GABA neurons have recently been found to be present in distinct subpopulations in the VTA. Opioids disrupt this regulation by inhibiting VTA GABA neurons via mu-opioid receptors (MORs), leading to increased DA activity and reinforcing drug-seeking behavior. However, the distribution of MORs across distinct VTA GABA subpopulations remains unclear. This study uses multiplexed in situ hybridization to map MOR (Oprm1) expression in genetically distinct GABA populations characterized by their expression of Pnoc, Crhbp, and Cbln4. Preliminary findings suggest differential Oprm1 expression, with Pnoc and Cbln4 populations showing high Oprm1 expression patterns, while Crhbp contains little Oprm1 expression. These results highlight the heterogeneity of VTA GABAergic neurons and provide insight into the mechanisms underlying opioid addiction, which may inform future therapeutic strategies.

Dopaminergic signaling within the striatum plays a crucial role in modulating reward and aversion, shaping behaviors such as food-seeking and consumption. While striatal dopamine release has been implicated in reinforcement learning and decision-making, the spatial and temporal dynamics of dopaminergic activity along the anterior-posterior axis of the striatum during consummatory behavior remain poorly understood. We investigated the role of dopamine in the striatum during the consumption of multiple solutions by employing a trial-based multi-spout behavioral paradigm with head fixed mice. To record the dopamine activity in the ventral and dorsal striatum, we utilized multi-site fiber photometry to record the fluorescent biosensor GRAB-DA2m along the anterior-posterior axis. Food restricted mice were given varying concentrations of sucrose as rewarding stimuli, while water restricted mice were given varying concentrations of sodium chloride as aversive stimuli. Our results revealed that dopamine responses scaled more across concentrations in the anterior regions of the striatum compared to the posterior regions. Additionally, we found more distinction between dopamine responses for the various concentrations of the aversive solution compared to the rewarding solution. Lastly, posterior striatal dopamine responses had a more rapid onset upon stimulus consumption, whereas anterior regions exhibited delayed responses, highlighting region-specific temporal differences in dopaminergic encoding. These findings refine our understanding of dopaminergic circuitry within the striatum and how dopamine-mediated responses to rewarding and aversive stimuli regulate feeding behaviors. By exploring this pathway, we offer potential insights into the mechanisms underlying disorders characterized by dysregulated reward including eating disorders and obesity.    

Disruptions in the mechanisms underlying threat detection and maladaptive aggressive behaviors are core features of several psychiatric disorders, including anxiety disorders and post-traumatic stress disorder (PTSD). In these conditions, heightened vigilance and attentional biases toward perceived threats can contribute to inappropriate aggression or avoidance behaviors, underscoring the need to understand the neural mechanisms mediating threat assessment and aggressive responses. We aim to better understand threat assessment and responding by interrogating brain region and cell-type specific activity patterns during unfamiliar social encounters using mice as our model system. Recent studies have identified the posterior paraventricular thalamus (pPVT) as a hub for processing sensory and emotional information in response to stress, predators, and other aversive contexts to facilitate a choice action. Despite its relevance, the role of pPVT in social-emotional brain circuit function remains unexplored. Recent transcriptomic datasets have revealed genetically identifiable clusters within PVT, specifically highlighting estrogen receptor-1 (Esr1) as a genetic marker for more posterior areas of PVT. In our behavior paradigm, mice with intact pPVT^Esr1 neural activity selectively attack novel conspecifics with unfamiliar traits (out-group) but not those with familiar traits (in-group) when introduced into their home cage. Given this, we designed an experiment using chemogenetics, a technique that utilizes genetically engineered receptors (DREADDs) to modulate neural activity, to test the involvement of pPVT^Esr1 neurons during unfamiliar social encounters. We have found that selectively inhibiting pPVT^Esr1 neurons using Gi-DREADDs reverses attack behavior, suggesting a putative role for these neurons during threat assessment and response processes. To follow up on these results, we are selectively exciting these neurons using Gq-DREADDs to determine how increased excitatory activity within pPVT^Esr1 neurons affects aggressive behaviors towards in-group and out-group intruders. We hypothesize that chemogenetic excitation of pPVT^Esr1 neurons will increase aggressive behaviors toward intruder mice for the entirety of the trial.