Biology subjects

Rimorin, C.

Publications and source records attributed to Rimorin, C..

11 recordsLinked to original sources

bioRxiv2026

Multimodal characterization of variation in neuronal types in the mouse basal ganglia

AbstractThe basal ganglia (BG) are a set of topographically organized, interconnected structures that are pivotal for regulating volitional movement and other aspects of cognitive, motivational, and affective behavior. Recently generated taxonomies of transcriptomically-defined cell types (T-types) have revealed both fine-grained distinctions in gene expression between neurons in these structures as well as continuous transcriptomic variation across similar T-types1-9, which are both related to location within a structure. However, it remains unclear to what extent these and other cellular properties co-vary with each other. Therefore, we performed Patch-seq experiments10,11 on over 900 neurons in mouse brain slices from BG to provide an integrated view of the co-variation between gene expression, location, physiology, and morphology measured from the same neurons. Medium spiny neurons (MSNs) from both the direct and indirect pathways across the dorsal and ventral striatum follow a gene expression gradient that varies in a dorsolateral to ventromedial direction; we find that this gradient also corresponds with systematic differences in action potential kinetics and dendritic arborization. Our analysis also characterizes additional multimodal dimensions of MSN variation, such as those between direct and indirect pathway neurons and between matrix and striosome neurons. Furthermore, through comparison with Patch-seq data from macaque, we demonstrate that the relationship between the transcriptomic/spatial gradient and electrophysiological and morphological properties is conserved across these two species. We also find that properties of striatal interneurons, such as action potential kinetics, vary across the striatum in a manner consistent with the MSN gradient. Outside the striatum, our multimodal Patch-seq dataset from the globus pallidus, subthalamic nucleus, and substantia nigra enabled us to characterize transcriptomically-defined types and link them to prior descriptions of cell types in these structures. Finally, we examined to what extent the MSN transcriptomic/spatial gradient persisted across different stages of the BG circuit by comparing Patch-seq neurons to reconstructed whole-neuron morphologies and the topography of their interareal projections, finding that the gradient is better preserved in GPe and GPi compared to SNr. Our study links transcriptomic variation across T-types in mouse BG to spatial localization and phenotypic differences at the level of individual cells, improving our understanding of cell type architecture in topographically organized circuits of the brain.

neuroscience↗

bioRxiv2026

The External Globus Pallidus is a Basal Ganglia Output Hub with Action-Specific Circuits

The external globus pallidus (GPe) is traditionally viewed as a homogeneous relay in the indirect basal ganglia pathway that broadly suppresses movement. Using whole-brain anterograde axon mapping, rabies tracing, single-neuron reconstruction, and single-nucleus RNA sequencing, we reveal that the GPe is a major basal ganglia output nucleus, composed of anatomically and molecularly distinct populations. Besides the neurons with canonical projections, and projections to striatum and cortex, the GPe contains specific neuronal populations that target the thalamus and brainstem directly, including the parafascicular thalamus (GPePf) and the pedunculopontine nucleus (GPePPN). These projection-defined subpopulations exhibit distinct behavioral functions. GPe-PPN neurons are selectively suppressed at locomotor onset, and bidirectional manipulation of this pathway is sufficient to promote or suppress locomotion. Notably, D2-MSN stimulation upstream of these neurons evokes locomotion, and co-activation of GPePPN pathway blocks this D2-MSN-evoked locomotion, demonstrating a disinhibitory circuit for action stemming from D2-MSNs. In contrast, GPePf neurons are not engaged during locomotion but are selectively recruited during skilled forelimb actions, and their activation disrupts forelimb movements without affecting locomotion. Together, these findings establish the GPe as a basal ganglia output hub composed of modules that mediate distinct behaviors. This organization revises canonical models of the indirect pathway by demonstrating that D2-MSNs can also facilitate, rather than only suppress, movement depending on the downstream GPe output channels they engage. In briefThe external globus pallidus (GPe), classically considered a relatively homogeneous relay within the indirect basal ganglia pathway, is revealed here as a major basal ganglia output hub. Distinct GPe subpopulations, defined by transcriptomic identity and projection target, form parallel channels to cortical, thalamic and brainstem structures with action-specific functions. These findings uncover a disinhibitory mechanism through which D2-MSNs can facilitate behavior, revising canonical models of basal ganglia function. HighlightsBrain-wide mapping reveals the GPe as a major basal ganglia output node GPe contains novel cell types defined by transcriptomic identity and projection specificity Projection-specific GPe circuits differentially control locomotion and skilled forelimb actions D2-MSNs can disinhibit downstream targets via specific GPe projections and promote action.

neuroscience↗

bioRxiv2026

A consensus spinal cord cell type atlas across mouse, macaque, and human

The spinal cord contains evolutionarily conserved cell types critical for motor function, sensory processing, and autonomic regulation, many of which are implicated in diverse neurological diseases and injuries. Yet the field lacks a comprehensive molecular characterization of cellular diversity in human, macaque, and mouse spinal cord. Here, we present a unified, cross-species cell type atlas based on the integration of single-nucleus gene expression, chromatin accessibility, and spatial transcriptomic data from segments within cervical, thoracic, lumbar, and sacral regions, including motor neurons (MNs) sampled across the entire rostro-caudal axis of the macaque spinal cord. Leveraging the spatial distributions of our molecularly defined cell types, we generated a cell type-guided anatomical map of spinal cord laminae and nuclei. We identified both conserved and species-specific cellular features, including gene expression patterns across distinct MN subtypes in the primate spinal cord. Cross-species cis-regulatory analysis and deep learning sequence models dissected the enhancer logic underlying viral targeting, uncovering conserved transcription factor grammar encoding cellular identity. Together, these results establish a unifying molecular and anatomical taxonomy of spinal cord cell types across species.

neuroscience↗

bioRxiv2023

Enhancer-AAVs allow genetic access to oligodendrocytes and diverse populations of astrocytes across species

Proper brain function requires the assembly and function of diverse populations of neurons and glia. Single cell gene expression studies have mostly focused on characterization of neuronal cell diversity; however, recent studies have also revealed substantial diversity of glial cells, particularly astrocytes. To better understand glial cell types and their roles in neurobiology, we built a new suite of adeno-associated viral (AAV)-based genetic tools to enable genetic access to astrocytes and oligodendrocytes. These oligodendrocyte and astrocyte enhancer-AAVs are highly specific (usually > 95% cell type specificity) with variable expression levels, and the astrocyte enhancer-AAVs show multiple distinct expression patterns reflecting the spatial distribution of astrocyte cell types. To provide the best glial-specific functional tools, several enhancer-AAVs were: optimized for higher expression levels, shown to be functional and specific in rat and macaque, shown to maintain specific activity across transgenes and in epilepsy where traditional promoters changed activity, and used to drive functional transgenes in astrocytes including Cre recombinase and acetylcholine-responsive sensor iAChSnFR. The astrocyte-specific iAChSnFR revealed a clear reward-dependent acetylcholine response in astrocytes of the nucleus accumbens during reinforcement learning. Together, this collection of glial enhancer-AAVs will enable characterization of astrocyte and oligodendrocyte populations and their roles across species, disease states, and behavioral epochs.

neuroscience↗

bioRxiv2023

A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain

The mammalian brain is composed of millions to billions of cells that are organized into numerous cell types with specific spatial distribution patterns and structural and functional properties. An essential step towards understanding brain function is to obtain a parts list, i.e., a catalog of cell types, of the brain. Here, we report a comprehensive and high-resolution transcriptomic and spatial cell type atlas for the whole adult mouse brain. The cell type atlas was created based on the combination of two single-cell-level, whole-brain-scale datasets: a single- cell RNA-sequencing (scRNA-seq) dataset of [~]7 million cells profiled, and a spatially resolved transcriptomic dataset of [~]4.3 million cells using MERFISH. The atlas is hierarchically organized into five nested levels of classification: 7 divisions, 32 classes, 306 subclasses, 1,045 supertypes and 5,200 clusters. We systematically analyzed the neuronal, non-neuronal, and immature neuronal cell types across the brain and identified a high degree of correspondence between transcriptomic identity and spatial specificity for each cell type. The results reveal unique features of cell type organization in different brain regions, in particular, a dichotomy between the dorsal and ventral parts of the brain: the dorsal part contains relatively fewer yet highly divergent neuronal types, whereas the ventral part contains more numerous neuronal types that are more closely related to each other. We also systematically characterized cell-type specific expression of neurotransmitters, neuropeptides, and transcription factors. The study uncovered extraordinary diversity and heterogeneity in neurotransmitter and neuropeptide expression and co-expression patterns in different cell types across the brain, suggesting they mediate a myriad of modes of intercellular communications. Finally, we found that transcription factors are major determinants of cell type classification in the adult mouse brain and identified a combinatorial transcription factor code that defines cell types across all parts of the brain. The whole-mouse-brain transcriptomic and spatial cell type atlas establishes a benchmark reference atlas and a foundational resource for deep and integrative investigations of cell type and circuit function, development, and evolution of the mammalian brain.

neuroscience↗

bioRxiv2022

Transcriptomic cytoarchitecture reveals principles of human neocortex organization

Variation in cortical cytoarchitecture is the basis for histology-based definition of cortical areas, such as Brodmann areas. Single cell transcriptomics enables higher-resolution characterization of cell types in human cortex, which we used to revisit the idea of the canonical cortical microcircuit and to understand functional areal specialization. Deeply sampled single nucleus RNA-sequencing of eight cortical areas spanning cortical structural variation showed highly consistent cellular makeup for 24 coarse cell subclasses. However, proportions of excitatory neuron subclasses varied strikingly, reflecting differences in intra- and extracortical connectivity across primary sensorimotor and association cortices. Astrocytes and oligodendrocytes also showed differences in laminar organization across areas. Primary visual cortex showed dramatically different organization, including major differences in the ratios of excitatory to inhibitory neurons, expansion of layer 4 excitatory neuron types and specialized inhibitory neurons. Finally, gene expression variation in conserved neuron subclasses predicts differences in synaptic function across areas. Together these results provide a refined cellular and molecular characterization of human cortical cytoarchitecture that reflects functional connectivity and predicts areal specialization.

neuroscience↗

bioRxiv2022

Comparative transcriptomics reveals human-specific cortical features

Humans have unique cognitive abilities among primates, including language, but their molecular, cellular, and circuit substrates are poorly understood. We used comparative single nucleus transcriptomics in adult humans, chimpanzees, gorillas, rhesus macaques, and common marmosets from the middle temporal gyrus (MTG) to understand human-specific features of cellular and molecular organization. Human, chimpanzee, and gorilla MTG showed highly similar cell type composition and laminar organization, and a large shift in proportions of deep layer intratelencephalic-projecting neurons compared to macaque and marmoset. Species differences in gene expression generally mirrored evolutionary distance and were seen in all cell types, although chimpanzees were more similar to gorillas than humans, consistent with faster divergence along the human lineage. Microglia, astrocytes, and oligodendrocytes showed accelerated gene expression changes compared to neurons or oligodendrocyte precursor cells, indicating either relaxed evolutionary constraints or positive selection in these cell types. Only a few hundred genes showed human-specific patterning in all or specific cell types, and were significantly enriched near human accelerated regions (HARs) and conserved deletions (hCONDELS) and in cell adhesion and intercellular signaling pathways. These results suggest that relatively few cellular and molecular changes uniquely define adult human cortical structure, particularly by affecting circuit connectivity and glial cell function.

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bioRxiv2020

A taxonomy of transcriptomic cell types across the isocortex and hippocampal formation

The isocortex and hippocampal formation are two major structures in the mammalian brain that play critical roles in perception, cognition, emotion and learning. Both structures contain multiple regions, for many of which the cellular composition is still poorly understood. In this study, we used two complementary single-cell RNA-sequencing approaches, SMART-Seq and 10x, to profile [~]1.2 million cells covering all regions in the adult mouse isocortex and hippocampal formation, and derived a cell type taxonomy comprising 379 transcriptomic types. The completeness of coverage enabled us to define gene expression variations across the entire spatial landscape without significant gaps. We found that cell types are organized in a hierarchical manner and exhibit varying degrees of discrete or continuous relatedness with each other. Such molecular relationships correlate strongly with the spatial distribution patterns of the cell types, which can be region-specific, or shared across multiple regions, or part of one or more gradients along with other cell types. Glutamatergic neuron types have much greater diversity than GABAergic neuron types, both molecularly and spatially, and they define regional identities as well as inter-region relationships. For example, we found that glutamatergic cell types between the isocortex and hippocampal formation are highly distinct from each other yet possess shared molecular signatures and corresponding layer specificities, indicating their homologous relationships. Overall, our study establishes a molecular architecture of the mammalian isocortex and hippocampal formation for the first time, and begins to shed light on its underlying relationship with the development, evolution, connectivity and function of these two brain structures.

neuroscience↗

bioRxiv2018

Conserved cell types with divergent features between human and mouse cortex

Elucidating the cellular architecture of the human neocortex is central to understanding our cognitive abilities and susceptibility to disease. Here we applied single nucleus RNA-sequencing to perform a comprehensive analysis of cell types in the middle temporal gyrus of human cerebral cortex. We identify a highly diverse set of excitatory and inhibitory neuronal types that are mostly sparse, with excitatory types being less layer-restricted than expected. Comparison to a similar mouse cortex single cell RNA-sequencing dataset revealed a surprisingly well-conserved cellular architecture that enables matching of homologous types and predictions of human cell type properties. Despite this general conservation, we also find extensive differences between homologous human and mouse cell types, including dramatic alterations in proportions, laminar distributions, gene expression, and morphology. These species-specific features emphasize the importance of directly studying human brain.

neuroscience↗

bioRxiv2017

Equivalent high-resolution identification of neuronal cell types with single-nucleus and single-cell RNA-sequencing

Transcriptional profiling of complex tissues by RNA-sequencing of single nuclei presents some advantages over whole cell analysis. It enables unbiased cellular coverage, lack of cell isolation-based transcriptional effects, and application to archived frozen specimens. Using a well-matched pair of single-nucleus RNA-seq (snRNA-seq) and single-cell RNA-seq (scRNA-seq) SMART-Seq v4 datasets from mouse visual cortex, we demonstrate that similarly high-resolution clustering of closely related neuronal types can be achieved with both methods if intronic sequences are included in nuclear RNA-seq analysis. More transcripts are detected in individual whole cells (~11,000 genes) than nuclei (~7,000 genes), but the majority of genes have similar detection across cells and nuclei. We estimate that the nuclear proportion of total cellular mRNA varies from 20% to over 50% for large and small pyramidal neurons, respectively. Together, these results illustrate the high information content of nuclear RNA for characterization of cellular diversity in brain tissues.

neuroscience↗

bioRxiv2017

Shared and distinct transcriptomic cell types across neocortical areas

Neocortex contains a multitude of cell types segregated into layers and functionally distinct regions. To investigate the diversity of cell types across the mouse neocortex, we analyzed 12,714 cells from the primary visual cortex (VISp), and 9,035 cells from the anterior lateral motor cortex (ALM) by deep single-cell RNA-sequencing (scRNA-seq), identifying 116 transcriptomic cell types. These two regions represent distant poles of the neocortex and perform distinct functions. We define 50 inhibitory transcriptomic cell types, all of which are shared across both cortical regions. In contrast, 49 of 52 excitatory transcriptomic types were found in either VISp or ALM, with only three present in both. By combining single cell RNA-seq and retrograde labeling, we demonstrate correspondence between excitatory transcriptomic types and their region-specific long-range target specificity. This study establishes a combined transcriptomic and projectional taxonomy of cortical cell types from functionally distinct regions of the mouse cortex.

neuroscience↗