Whole-body and Whole-Organ Clearing and Imaging Techniques with Single-Cell Resolution: Toward Organism-Level Systems Biology in Mammals

Cell chemical biology, Journal Year: 2016, Volume and Issue: 23(1), P. 137 - 157

Published: Jan. 1, 2016

Language: Английский

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Whole-brain mapping of the direct inputs and axonal projections of POMC and AgRP neurons

Frontiers in Neuroanatomy, Journal Year: 2015, Volume and Issue: 9

Published: March 27, 2015

Pro-opiomelanocortin (POMC) neurons in the arcuate nucleus (ARC) of hypothalamus and tractus solitarius (NTS) brainstem play important roles suppressing food intake maintaining energy homeostasis. Previous tract-tracing studies have revealed axonal connection patterns these two brain areas, but intermingling POMC with other neuron types has made it challenging to precisely identify inputs outputs neurons. In this study, we used modified rabies virus map areas that provide direct ARC NTS as well AgRP for comparison. receive from dozens discrete structures throughout forebrain brainstem. The containing presynaptic partners largely overlap those neurons, although relatively broader, denser inputs. Furthermore, predominantly show very different innervation ARC. By selectively expressing fluorescent markers found almost all their major are innervated by suggesting there strong reciprocal projections among neural pathways. comprehensively chartering whole-brain connections central melanocortin system a cell-type-specific manner, study lays foundation dissecting underlying circuit mechanisms specific pathways regulating

Language: Английский

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Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei

eLife, Journal Year: 2019, Volume and Issue: 8

Published: Oct. 24, 2019

Serotonin neurons of the dorsal and median raphe nuclei (DR, MR) collectively innervate entire forebrain midbrain, modulating diverse physiology behavior. To gain a fundamental understanding their molecular heterogeneity, we used plate-based single-cell RNA-sequencing to generate comprehensive dataset comprising eleven transcriptomically distinct serotonin neuron clusters. Systematic in situ hybridization mapped specific clusters principal DR, caudal or MR. These transcriptomic differentially express rich repertoire neuropeptides, receptors, ion channels, transcription factors. We generated novel intersectional viral-genetic tools access subpopulations. Whole-brain axonal projection mapping revealed that DR co-expressing vesicular glutamate transporter-3 preferentially cortex, whereas those thyrotropin-releasing hormone subcortical regions particular hypothalamus. Reconstruction 50 individual segregated patterns at level. Together, these results provide foundation heterogenous neuronal phenotypes.

Language: Английский

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Embracing diversity in the 5-HT neuronal system

Nature reviews. Neuroscience, Journal Year: 2019, Volume and Issue: 20(7), P. 397 - 424

Published: April 4, 2019

Language: Английский

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An interactive framework for whole-brain maps at cellular resolution

Nature Neuroscience, Journal Year: 2017, Volume and Issue: 21(1), P. 139 - 149

Published: Dec. 2, 2017

Language: Английский

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The Input-Output Relationship of the Cholinergic Basal Forebrain

Cell Reports, Journal Year: 2017, Volume and Issue: 18(7), P. 1817 - 1830

Published: Feb. 1, 2017

Basal forebrain cholinergic neurons influence cortical state, plasticity, learning, and attention. They collectively innervate the entire cerebral cortex, differentially controlling acetylcholine efflux across different areas timescales. Such control might be achieved by differential inputs driving separable outputs, although no input-output relationship on a brain-wide level has ever been demonstrated. Here, we identify input to cells projecting specific regions infecting axon terminals with monosynaptically restricted viral tracer. This approach revealed several circuit motifs, such as central amygdala synapsing onto basolateral amygdala-projecting or strong somatosensory motor cortex-projecting neurons. The presence of in parasympathetic midbrain nuclei contacting frontally suggest that network regulating inner eye muscles are additionally state via efflux. dataset enables future circuit-level experiments drivers known functions.

Language: Английский

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Reward and Aversion

Annual Review of Neuroscience, Journal Year: 2016, Volume and Issue: 39(1), P. 297 - 324

Published: May 5, 2016

To benefit from opportunities and cope with challenges in the environment, animals must adapt their behavior to acquire rewards avoid punishments. Maladaptive changes neuromodulatory systems neural circuits for reward aversion can lead manifestation of several prominent psychiatric disorders including addiction depression. Recent progress is pushing boundaries knowledge on two major fronts research aversion: First, new layers complexity have been reported functions dopamine (DA) serotonin (5-HT) aversion. Second, specific circuit components pathways that encode begun be identified. This review aims outline historic perspectives insights into DA 5-HT coding distinct rewards. It also highlights recent advances studies enabled by technologies, such as cell-type-specific electrophysiology tracing, optogenetics-based behavioral manipulation. may provide guidance developing novel treatment strategies neuropsychiatric diseases related malfunction system.

Language: Английский

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The Roles of Serotonin in Neuropsychiatric Disorders

Cellular and Molecular Neurobiology, Journal Year: 2021, Volume and Issue: 42(6), P. 1671 - 1692

Published: March 2, 2021

Language: Английский

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Development of prefrontal cortex

Neuropsychopharmacology, Journal Year: 2021, Volume and Issue: 47(1), P. 41 - 57

Published: Oct. 13, 2021

Abstract During evolution, the cerebral cortex advances by increasing in surface and introduction of new cytoarchitectonic areas among which prefrontal (PFC) is considered to be substrate highest cognitive functions. Although neurons PFC are generated before birth, differentiation its development synaptic connections humans extend 3rd decade life. this period, synapses as well neurotransmitter systems including their receptors transporters, initially overproduced followed selective elimination. Advanced methods applied human animal models, enable investigation cellular mechanisms role specific genes, non-coding regulatory elements signaling molecules control neuronal production phenotypic fate, migration establish layering PFC. Likewise, various genetic approaches combination with functional assays immunohistochemical imaging reveal roles during maturation Disruption, or even a slight slowing rate production, synaptogenesis environmental factors, can induce gross subtle changes that eventually lead impairment. An understanding evolution provide insight into pathogenesis treatment congenital neuropsychiatric diseases idiopathic developmental disorders cause intellectual disabilities.

Language: Английский

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A whole-brain atlas of monosynaptic input targeting four different cell types in the medial prefrontal cortex of the mouse

Nature Neuroscience, Journal Year: 2019, Volume and Issue: 22(4), P. 657 - 668

Published: March 18, 2019

Language: Английский

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