Biology subjects

Simon, R. C.

Publications and source records attributed to Simon, R. C..

4 recordsLinked to original sources

bioRxiv2025

Mu opioid receptor mRNA and protein localization across the rat and mouse habenula

The habenula (Hb) has high intensity mu opioid binding and receptor (MOR) expression. It contains medial and lateral subdivisions (MHb and LHb, respectively), yet the details of MOR localization across these regions remains debated. MHb and LHb participate in largely non-overlapping neural circuits, therefore accurately resolving MOR expression across them is critical for understanding how MOR ligands impact behaviors. Here we utilized in situ hybridization (ISH) and immunocytochemistry (ICC) to systematically map Oprm1 mRNA and MOR protein throughout the habenular complex. We studied rat and mouse tissue to evaluate expression across two common research species. We also performed parallel mapping in Oprm1-Venus/Venus mice. Importantly, we found mRNA and protein in both MHb and LHb in both species. In rat, 39 {+/-} 3% and 21 {+/-} 4% of cells expressed Oprm1 in MHb and LHb, respectively. These proportions were greater in mouse: 57 {+/-} 1% (MHb) and 32 {+/-} 4% (LHb). Oprm1 puncta per positive cell were greater in MHb compared to LHb for both rat and mouse (p < 0.0001). The highest intensity labeling was localized along the lateral edge of the MHb for all methods. ICC showed MOR localized to fibers and somata in both regions. In LHb, MOR labeling was most dense in intermediate sections along the anterior-posterior (AP) axis. In rats we also observed greater labeling in dorsal LHb at intermediate AP levels and medial LHb more posteriorly. These results indicate that both MHb and LHb can contribute to MOR mediated actions through their respective circuits. Key PointsO_LIMu opioid receptor mRNA and protein are expressed in both the medial and lateral habenulae in rat and mouse. C_LIO_LIIn the medial habenula, most mu opioid receptor mRNA and protein was detected along its lateral border. C_LIO_LIAcross samples, Oprm1+ cells in the MHb contained more mRNA puncta per cell compared to lateral habenula cells. C_LI

neuroscience↗

bioRxiv2024

Single-cell sequencing of rodent ventral pallidum reveals diverse neuronal subtypes with non-canonical interregional continuity

The ventral pallidum (VP) was defined as a basal ganglia nucleus with dense input from ventral striatum. To further investigate a VP regional identity, we conducted a cross-species transcriptional characterization of VP cell types. We performed single nucleus RNA-sequencing of VP tissue from mice and rats and identified 16 VP neuronal subclasses with striking cross-species conservation. VP GABAergic neurons were surprisingly heterogeneous, consisting of 14 sub-classes from 3 developmental classes. Combining our sequencing data with a spatial atlas revealed that all VP subclasses extended beyond the traditional borders of VP. Integrating our VP data with prior sequencing data from striatal, hypothalamic, and extended amygdalar tissue confirmed that cell types are shared among these regions. Due to the role of VP in feeding behavior, we also assessed the transcriptional impact of high-fat diet consumption, which induced altered expression of genes involved in oxidative phosphorylation and inhibitory signaling. Overall, our results demonstrate that VP is not a transcriptionally discrete nucleus; rather, VP contains cell types with diverse expression patterns that overlap with regions beyond the basal ganglia.

neuroscience↗

bioRxiv2023

Opto-seq reveals input-specific immediate early gene induction in ventral tegmental area cell types

The ventral tegmental area (VTA) is a critical node in circuits governing motivated behavior and is home to diverse populations of neurons that release dopamine, GABA, glutamate, or combinations of these neurotransmitters. The VTA receives inputs from many brain regions, but a comprehensive understanding of input-specific activation of VTA neuronal subpopulations is lacking. To address this, we combined optogenetic stimulation of select VTA inputs with single-nucleus RNA sequencing (snRNAseq) and highly multiplexed in situ hybridization to identify distinct neuronal clusters and characterize their spatial distribution and activation patterns. Quantification of immediate early gene (IEG) expression revealed that different inputs activated select VTA subpopulations, which demonstrated cell-type specific IEG programs. Within dopaminergic subpopulations IEG induction levels correlated with differential expression of ion channel genes. This new transcriptomics-guided circuit analysis reveals the diversity of VTA activation driven by distinct inputs and provides a resource for future analysis of VTA cell types.

neuroscience↗

bioRxiv2022

A diverse network of pericoerulear neurons control arousal states

As the primary source of norepinephrine (NE) in the brain, the locus coeruleus (LC) regulates arousal, avoidance and stress responses1,2. However, how local neuromodulatory inputs control LC function remains unresolved. Here we identify a population of transcriptionally, spatially and functionally diverse GABAergic neurons in the LC dendritic field that receive distant inputs and modulate modes of LC firing to control global arousal levels and arousal-related processing and behaviors. We define peri-LC anatomy using viral tracing and combine single-cell RNA sequencing with spatial transcriptomics to molecularly define both LC-NE and peri-LC cell types. We identify several neuronal cell types which underlie peri-LC functional diversity using a series of complementary neural circuit approaches in behaving mice. Our findings indicate that LC and peri-LC neurons are transcriptionally, functionally, and anatomically heterogenous neuronal populations which modulate arousal and avoidance states. Defining the molecular, cellular, and functional diversity of the LC and peri-LC provides a road map for understanding the neurobiological basis of arousal, motivation and neuropsychiatric disorders.

neuroscience↗