Biology subjects

Weglage, M.

Publications and source records attributed to Weglage, M..

3 recordsLinked to original sources

bioRxiv2022

Esr1+ hypothalamic-habenula neurons shape aversive states.

Excitatory projections from the lateral hypothalamic area (LHA) to the lateral habenula (LHb) drive aversive responses. We used Patch-seq guided multimodal classification to define the structural and functional heterogeneity of the LHA-LHb pathway. Our classification identified six glutamatergic neuron types with unique electrophysiological properties, molecular profiles, and projection patterns. We found that genetically-defined LHA-LHb neurons signal distinct aspects of emotional or naturalistic behaviors: Esr1+ LHA-LHb neurons induce aversion, whereas Npy+ LHA-LHb neurons control rearing behavior. Repeated optogenetic drive of Esr1+ LHA-LHb neurons induces a behaviorally persistent aversive state, and large-scale recordings showed a region-specific neural representation of the aversive state in the prelimbic region of the prefrontal cortex. We further found that exposure to unpredictable mild shocks induced a sex-specific sensitivity to develop a stress state in female mice, which was associated with a specific shift in the intrinsic properties of bursting-type Esr1+ LHA-LHb neurons. In summary, we describe the diversity of LHA-LHb neuron types, and provide evidence for the role of Esr1+ neurons in aversion and sexually dimorphic stress sensitivity.

neuroscience↗

bioRxiv2022

Sst+ GPi output neurons provide direct feedback to key nodes of the basal ganglia and drive behavioral flexibility.

The internal globus pallidus (GPi) is a basal ganglia output nucleus with separate projections to the thalamus and the lateral habenula (LHb). Here, we show a GPi subtype with projections to LHb (GPi-LHb), genetically defined based on glutamate/GABA co-transmission and somatostatin (Sst) expression, also projects back to key nodes in the basal ganglia: the external globus pallidus (GPe), the striatal striosomes, and dopamine neurons in the substantia nigra. We found that the Sst+ GPi population showed strong movement and direction-specific selectivity in a goal-directed choice task, but not during self-paced exploration, and did not signal prediction errors or outcome modulation. During goal-directed behavior, the Sst+ GPi activity slowly evolved with learning of correct choice actions and genetic silencing disrupted the ability to update choice behavior following a task rule reversal. In summary, we have found that Sst+ GPi neurons establish a wide feedback network in the basal ganglia and drive behavioral flexibility.

neuroscience↗

bioRxiv2020

Complete representation of action space and value in all striatal pathways.

The dorsal striatum plays a central role in motor and decision programs, such as the selection and execution of particular actions and the evaluation of their outcomes. A standard model has emerged where distinct output pathways encode separate motor-action signals, including selection-evaluation division in the matrix versus patch compartments. We used large-scale cell-type specific calcium imaging during motor and decision behaviors to determine and contrast the activity of individual striatal projection neurons (SPNs) belonging to one of the three major output pathways in the dorsomedial striatum - patch Oprm1+ SPNs versus the D1+ direct and A2A+ indirect pathway. We found that Oprm1+ SPNs were tuned to a number of different behavioral categories, such as to different movements, or to discrete actions and decisions in a two-choice task, and these complex representations were found to the same extent in all three striatal output pathways. The sharp tuning of individual SPNs was highly stereotyped over time while performing a specific task, but the tuning profile remapped between different behavioral contexts. In addition to action representations, SPNs showed pathway-independent representation of decision-variables such as the trial strategy and the action value. We propose that all three major output pathways in the dorsomedial striatum share a similarly complete representation of the entire action space, including task- and phase-specific signals of action value and choice.

neuroscience↗