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Bardenhewer, R.

Publications and source records attributed to Bardenhewer, R..

2 recordsLinked to original sources

Topographically organized dorsal raphe activity modulates forebrain sensory-motor computations and adaptive behaviors.

The dorsal raphe nucleus (DRN) plays an important role in shaping a wide range of behaviors, including mood, motivation, appetite, sleep, and social interactions. Reflecting these diverse roles, the DRN is composed of molecularly distinct and topographically organized groups of neurons that target specific regions of the forebrain. Despite these insights, fundamental questions remain regarding how DRN neurons process sensory information, what do DRN communicate to forebrain, and the role of DRN inputs in forebrain computations and animal behavior. To address these questions, we investigated the spatiotemporal activity patterns of DRN neurons, along with DRN axons and their targets in the juvenile zebrafish forebrain. Our findings revealed a remarkable topographic organization of ongoing activity and sensory-motor responses within the DRN. We discovered that a large fraction of DRN neurons are primarily driven by animals locomotor activity. We also observed that an anterior group of DRN neurons, marked by Gad1, exhibited distinct activity patterns during rest, locomotor activity and sensory stimulation. DRN axons broadly innervating the forebrain exhibit topographically organized excitation and inhibition in response to sensory stimulation and motor activity. Notably, we observed significant and rapid covariation between the activity of DRN axons and nearby forebrain neurons. Chemogenetic ablation of the DRN led to a marked reduction in the synchrony and sensory-motor responses across forebrain neurons, accompanied by significant deficits in adaptive behaviors. Collectively, our findings revealed the functional diversity of DRN neurons and their role in transmitting sensory and locomotor signals via topographically organized projections, which can regulate forebrain activity and play a crucial role in modulating animal behavior.

neuroscience↗

Inhibition mediated by group III mGluRs regulates habenula activity and defensive behaviors

Inhibition contributes to various brain computations from sensory motor transformations to cognitive operations. While most studies on inhibition focus on GABA, the main excitatory neurotransmitter of the brain, glutamate, can also elicit inhibition via metabotropic glutamate receptors (mGluRs). The function of mGluR-mediated inhibition remains largely elusive. Here, we investigated the role of group III mGluR-dependent inhibition in the habenula. This primarily glutamatergic and conserved forebrain region acts as a hub between multiple forebrain inputs and neuromodulatory mid- and hindbrain targets that regulate adaptive behaviors. We showed that both zebrafish and mice habenula express group III mGluRs. We identified that group III mGluRs regulate the membrane potential and calcium activity of zebrafish dorsal habenula. Pharmacological and genetic perturbation of group III mGluRs increased sensory-evoked excitation and reduced selectivity of habenular neurons to different sensory modalities. We also observed that inhibition is the main channel of communication between primarily glutamatergic habenula neurons. Blocking group III mGluRs reduced inhibition within habenula and increased correlations during spontaneous activity. In line with such inhibition within habenula, we identified that multi-sensory information is integrated mainly through competition and suppression across habenular neurons, which in part relies on group III mGluRs. Finally, genetic perturbation of a habenula-specific group III mGluR, mGluR6a, amplified neural responses and defensive behaviors evoked by sensory stimulation and environmental changes. Altogether, our results revealed that mGluR driven inhibition is essential in encoding, integration, and communication of information between Hb neurons, ultimately playing a critical role in regulating defensive and adaptive behaviors.

neuroscience↗