Biology subjects

Stujenske, J. M.

Publications and source records attributed to Stujenske, J. M..

4 recordsLinked to original sources

bioRxiv2026

Cell-type-specific encoding of effort-based decision-making in the dorsal raphe nucleus

Effort-based decision-making, the process of weighing reward benefits against effort costs, is essential for adaptive behavior. Although the dorsal raphe nucleus (DRN) contributes to reward processing and effort-related behaviors, how specific DRN neuronal subtypes contribute to effort-based decision-making remains poorly understood. Using fiber photometry to record DRN serotonergic and GABAergic neurons during an effort-based decision-making task, we found that tonic fluctuations in DRN serotonergic activity were selectively associated with persistent selection of the high-value option. Furthermore, we found that while neither neuronal population was sensitive to relative reward magnitude, effort expenditure selectively enhanced decision- and reward-related signals carried by serotonergic and GABAergic neurons, respectively. Together, these findings support a cell type-specific model in which serotonergic activity provides a signal linking persistent motivational states to effortful choice, whereas GABAergic activity may contribute to evaluating or updating reward outcomes after effort expenditure. SIGNIFICANCE STATEMENTChoosing whether a reward is worth the effort required to obtain it is essential for adaptive behavior, yet the neural mechanisms underlying this process remain incompletely understood. Here, we identify distinct contributions of serotonin- and GABAergic neurons in the dorsal raphe nucleus, a major source of brain serotonin, to effort-based decision-making. Serotonergic neurons were preferentially engaged in sustained motivational state and action selection, and GABAergic neurons in the processing of reward outcomes following costly actions. Our findings reveal a cell type-specific organization of effort-based reward seeking in the dorsal raphe nucleus and provide a framework for understanding how motivational states, decisions, and reward outcomes are coordinated.

neuroscience↗

bioRxiv2026

Cellular and molecular coding of habit-driven behavior in the dorsal raphe nucleus

Chronic stress has potent effects on reward-seeking behavior, reducing hedonic drive but also biasing individuals toward habitual responding at the expense of goal-directed action. While prior studies have implicated corticostriatal circuits in these shifts, the contribution of the dorsal raphe nucleus (DRN) - a central neuromodulatory hub that regulates motivational states - remains poorly understood. Here, we identify a key role for DRN neurons in mediating stress-induced transitions from goal-directed to habit-driven behavior. Using two-photon calcium imaging in awake behaving mice, we show that DRN neurons encode representations of both effort expenditures and reward acquisition that are integrated at the single-neuron level. Chronic stress selectively enhances reward-related responses in habit-driven individuals, and deficits in reward-related activity in DRN neurons predict future habit formation after chronic stress. Single-nucleus transcriptional profiling revealed that chronic stress drives habit-related gene expression changes in GABAergic DRN neurons, including upregulation of genes implicated in synapse function and inhibitory signaling, and identified potential pharmacological treatment targets. Optogenetic inhibition of DRN GABA neurons rescued stress effects on habit formation, driving stable shifts in operant responding that persisted for days. Together, these findings establish the DRN as a critical modulator of stress-induced behavioral inflexibility, and identify a new role for DRN GABAergic neurons in determining stress susceptibility and driving stable and persistent switches in operant responding during recovery from chronic stress.

neuroscience↗

bioRxiv2024

Projection-Targeted Photopharmacology Reveals Distinct Anxiolytic Roles for Presynaptic mGluR2 in Prefrontal- and Insula-Amygdala Synapses

Dissecting how membrane receptors regulate neural circuit function is critical for deciphering basic principles of neuromodulation and mechanisms of therapeutic drug action. Classical pharmacological and genetic approaches are not well-equipped to untangle the roles of specific receptor populations, especially in long-range projections which coordinate communication between brain regions. Here we use viral tracing, electrophysiological, optogenetic, and photopharmacological approaches to determine how presynaptic metabotropic glutamate receptor 2 (mGluR2) activation in the basolateral amygdala (BLA) alters anxiety-related behavior. We find that mGluR2-expressing neurons from the ventromedial prefrontal cortex (vmPFC) and posterior insular cortex (pIC) preferentially target distinct cell types and subregions of the BLA to regulate different forms of avoidant behavior. Using projection-specific photopharmacological activation, we find that mGluR2-mediated presynaptic inhibition of vmPFC-BLA, but not pIC-BLA, connections can produce long-lasting decreases in spatial avoidance. In contrast, presynaptic inhibition of pIC-BLA connections decreased social avoidance, novelty-induced hypophagia, and increased exploratory behavior without impairing working memory, establishing this projection as a novel target for the treatment of anxiety disorders. Overall, this work reveals new aspects of BLA neuromodulation with therapeutic implications while establishing a powerful approach for optical mapping of drug action via photopharmacology. Highlights- Basolateral amygdala is a key site for anxiolytic action of mGluR2 agonism - BLA receives dense Grm2+ inputs from ventromedial prefrontal cortex and posterior insular cortex - Photoactivation of mGluR2 has distinct anxiolytic effects in vmPFC-BLA and pIC-BLA synapses - Grm2+ vmPFC and pIC projections target medial and lateral BLA subregions, respectively

neuroscience↗

bioRxiv2020

Prelimbic-dependent activation of amygdala somatostatin interneurons signals non-aversive cues to promote discrimination.

The amygdala and prelimbic cortex (PL) communicate during fear discrimination retrieval, but how they coordinate to discriminate a non-threatening stimulus is unknown. Here, we show that somatostatin interneurons (SOM) in the basolateral amygdala (BLA) become active specifically during learned non-threatening cues, when they block sensory-evoked phase resetting of theta-oscillations. Further, we show that SOM activation is PL-dependent, and promotes discrimination of non-threat. Thus, fear discrimination engages PL-dependent coordination of BLA SOM responses to non-threatening stimuli.

neuroscience↗