Nucleus accumbens circuit disinhibits lateral hypothalamus glutamatergic neurons contributing to morphine withdrawal memory in male mice DOI Creative Commons
Sheng Huan, Chao Lei, Yu Yuan

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Jan. 5, 2023

The lateral hypothalamus (LH) is physiologically critical in brain functions. LH also plays an important role drug addiction. However, neural circuits underlying involvement of addiction remain obscure. In the present study,our results showed that male mice, during context-induced expression morphine withdrawal memory, glutamatergic neurons played role; dopamine D1 receptor-expressing medium spiny (D1-MSNs) projecting from core nucleus accumbens (NAcC) to were upstream circuit activate neurons; D1-MSNs NAcC activated through inhibiting local gamma-aminobutyric acid (GABA) neurons. These suggest disinhibited by importantly contribute memory.

Language: Английский

Distinct reward processing by subregions of the nucleus accumbens DOI Creative Commons
Gaowei Chen,

Shishi Lai,

Guo Bin Bao

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(2), P. 112069 - 112069

Published: Feb. 1, 2023

The nucleus accumbens (NAc) plays an important role in motivation and reward processing. Recent studies suggest that different NAc subnuclei differentially contribute to reward-related behaviors. However, how is encoded individual neurons remains unclear. Using vivo single-cell resolution calcium imaging, we find diverse patterns of encoding the medial lateral shell subdivision (NAcMed NAcLat, respectively). Reward consumption increases NAcLat activity but decreases NAcMed activity, albeit with high variability among neurons. heterogeneity could be attributed differences their synaptic inputs transcriptional profiles. Specific optogenetic activation Nts-positive promotes positive reinforcement, while Cartpt-positive induces behavior aversion. Collectively, our study shows organizational subregions provides a framework for future dissection physiological pathological conditions.

Language: Английский

Citations

44
A molecularly defined and spatially resolved cell atlas of the whole mouse brain DOI Creative Commons
Meng Zhang, Xingjie Pan, Won Jung

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: March 7, 2023

In mammalian brains, tens of millions to billions cells form complex interaction networks enable a wide range functions. The enormous diversity and intricate organization in the brain have so far hindered our understanding molecular cellular basis its Recent advances spatially resolved single-cell transcriptomics allowed systematic mapping spatial molecularly defined cell types tissues1-3. However, these approaches only been applied few regions1-11 comprehensive atlas whole is still missing. Here, we imaged panel >1,100 genes ~8 million across entire adult mouse using multiplexed error-robust fluorescence situ hybridization (MERFISH)12 performed resolved, expression profiling at whole-transcriptome scale by integrating MERFISH RNA-sequencing (scRNA-seq) data. Using this approach, generated >5,000 transcriptionally distinct clusters, belonging ~300 major types, with high resolution. Registration images common coordinate framework (CCF) further quantifications composition individual regions CCF. We identified modules characterized cell-type compositions gradients featuring gradual changes gene-expression profiles cells. Finally, high-resolution map cells, transcriptome-wide profile associated each cell, us infer cell-type-specific interactions between several hundred pairs predict potential (ligand-receptor) functional implications cell-cell interactions. These results provide rich insights into architecture valuable resource for future investigations neural circuits their dysfunction diseases.

Language: Английский

Citations

43
Charting the cellular biogeography in colitis reveals fibroblast trajectories and coordinated spatial remodeling DOI
Paolo Cadinu, Kisha N. Sivanathan, A. Misra

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(8), P. 2010 - 2028.e30

Published: April 1, 2024

Language: Английский

Citations

28
The Insular Cortex: An Interface Between Sensation, Emotion and Cognition DOI
Ruohan Zhang, Hanfei Deng, Xiong Xiao

et al.

Neuroscience Bulletin, Journal Year: 2024, Volume and Issue: 40(11), P. 1763 - 1773

Published: May 9, 2024

Language: Английский

Citations

28
Drugs of abuse hijack a mesolimbic pathway that processes homeostatic need DOI
Bowen Tan, Caleb J. Browne, Tobias Nöbauer

et al.

Science, Journal Year: 2024, Volume and Issue: 384(6693)

Published: April 18, 2024

Drugs of abuse are thought to promote addiction in part by “hijacking” brain reward systems, but the underlying mechanisms remain undefined. Using whole-brain FOS mapping and vivo single-neuron calcium imaging, we found that drugs augment dopaminoceptive ensemble activity nucleus accumbens (NAc) disorganize overlapping responses natural rewards a cell type–specific manner. Combining FOS-Seq, CRISPR-perturbation, single-nucleus RNA sequencing, identified Rheb as molecular substrate regulates signal transduction NAc while enabling suppress consumption. Mapping NAc-projecting regions activated revealed input-specific effects on These findings characterize dynamic, circuit basis common pathway, wherein interfere with fulfillment innate needs.

Language: Английский

Citations

27
MENDER: fast and scalable tissue structure identification in spatial omics data DOI Creative Commons
Zhiyuan Yuan

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 5, 2024

Abstract Tissue structure identification is a crucial task in spatial omics data analysis, for which increasingly complex models, such as Graph Neural Networks and Bayesian networks, are employed. However, whether increased model complexity can effectively lead to improved performance notable question the field. Inspired by consistent observation of cellular neighborhood structures across various technologies, we propose Multi-range cEll coNtext DEciphereR (MENDER), tissue identification. Applied on datasets 3 brain regions whole-brain atlas, MENDER, with biology-driven design, offers substantial improvements over modern models while automatically aligning labels slices, despite using much less running time than second-fastest. MENDER’s power allows uncovering previously overlooked domains that exhibit strong associations aging. scalability makes it freely appliable million-level atlas. discriminative enables differentiation breast cancer patient subtypes obscured single-cell analysis.

Language: Английский

Citations

21
A spatially-resolved transcriptional atlas of the murine dorsal pons at single-cell resolution DOI Creative Commons
Stefano Nardone, Roberto De Luca,

Antonino Zito

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 4, 2024

Abstract The “dorsal pons”, or pontine tegmentum” (dPnTg), is part of the brainstem. It a complex, densely packed region whose nuclei are involved in regulating many vital functions. Notable among them parabrachial nucleus, Kölliker Fuse, Barrington locus coeruleus, and dorsal, laterodorsal, ventral tegmental nuclei. In this study, we applied single-nucleus RNA-seq (snRNA-seq) to resolve neuronal subtypes based on their unique transcriptional profiles then used multiplexed error robust fluorescence situ hybridization (MERFISH) map spatially. We sampled ~1 million cells across dPnTg defined spatial distribution over 120 subtypes. Our analysis identified an unpredicted high diversity pinpointed marker genes also demonstrated that transcriptionally similar between humans mice, enhancing study’s translational value. Finally, developed freely accessible, GPU CPU-powered dashboard ( http://harvard.heavy.ai:6273/ ) combines interactive visual analytics hardware-accelerated SQL into data science framework allow scientific community query gain insights data.

Language: Английский

Citations

18
Sequential transitions of male sexual behaviors driven by dual acetylcholine-dopamine dynamics DOI Creative Commons
Ai Miyasaka, Takeshi Kanda,

N. Nonaka

et al.

Neuron, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

The neural mechanisms underlying the sequential transitions of male sexual behaviors, including mounting, intromission, and ejaculation, remain largely unexplored. Here, we report that acetylcholine (ACh)-dopamine (DA) dynamics in ventral shell nucleus accumbens (vsNAc) regulate these mice. During vsNAc displays a unique pattern dual ACh-DA rhythms, generated by reciprocal regulation between ACh DA signaling via nicotinic receptors (nAChRs) D2 (D2Rs). Knockdown choline acetyltransferase (ChAT) or D2R diminishes occurrence intromission ejaculation. Optogenetic manipulations demonstrated maintains behaviors suppressing D2RvsNAc neurons. Moreover, promotes initiation mounting facilitates intromission-ejaculation transition inducing slowdown rhythm. Together, findings reveal coordinated play critical role orchestrating behaviors.

Language: Английский

Citations

2
Reward and aversion processing by input-defined parallel nucleus accumbens circuits in mice DOI Creative Commons
Kuikui Zhou, Hua Xu, Shanshan Lu

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Oct. 21, 2022

Abstract The nucleus accumbens (NAc) is critical in mediating reward seeking and also involved negative emotion processing, but the cellular circuitry mechanisms underlying such opposing behaviors remain elusive. Here, using recently developed AAV1-mediated anterograde transsynaptic tagging technique mice, we show that NAc neurons receiving basolateral amygdala inputs (NAc BLA ) promote positive reinforcement via disinhibiting dopamine ventral tegmental area (VTA). In contrast, paraventricular thalamic PVT innervate GABAergic lateral hypothalamus (LH) mediate aversion. Silencing synaptic output of impairs behavior, while silencing or →LH pathway abolishes aversive symptoms opiate withdrawal. Our results elucidate afferent-specific circuit architecture controlling

Language: Английский

Citations

66
Angiotensin-converting enzyme gates brain circuit–specific plasticity via an endogenous opioid DOI
Brian H. Trieu, Bailey C. Remmers, Carlee Toddes

et al.

Science, Journal Year: 2022, Volume and Issue: 375(6585), P. 1177 - 1182

Published: March 10, 2022

Angiotensin-converting enzyme (ACE) regulates blood pressure by cleaving angiotensin I to produce II. In the brain, ACE is especially abundant in striatal tissue, but function of circuits remains poorly understood. We found that degrades an unconventional enkephalin heptapeptide, Met-enkephalin-Arg-Phe, nucleus accumbens mice. inhibition enhanced µ-opioid receptor activation causing a cell type–specific long-term depression glutamate release onto medium spiny projection neurons expressing Drd1 dopamine receptor. Systemic was not intrinsically rewarding, it led decrease conditioned place preference caused fentanyl administration and enhancement reciprocal social interaction. Our results raise enticing prospect central can boost endogenous opioid signaling for clinical benefit while mitigating risk addiction.

Language: Английский

Citations

40