Neocortical somatostatin neuron diversity in cognition and learning

Trends in Neurosciences, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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An enhancer-AAV toolbox to target and manipulate distinct interneuron subtypes

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 22, 2024

SUMMARY In recent years, we and others have identified a number of enhancers that, when incorporated into rAAV vectors, can restrict the transgene expression to particular neuronal populations. Yet, viral tools access manipulate fine subtypes are still limited. Here, performed systematic analysis single cell genomic data identify enhancer candidates for each cortical interneuron subtypes. We established set enhancer-AAV that highly specific distinct populations striatal cholinergic neurons. These enhancers, used in context different effectors, target (fluorescent proteins), observe activity (GCaMP) (opto- or chemo-genetics) also validated our across species. Thus, provide field with powerful study neural circuits functions develop precise targeted therapy.

Язык: Английский

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Neocortical long-range inhibition promotes cortical synchrony and sleep

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 23, 2024

Behavioral states such as sleep and wake are highly correlated with specific patterns of rhythmic activity in the cortex. During low arousal slow wave sleep, cortex is synchronized dominated by frequency rhythms coordinated across multiple regions. Although recent evidence suggests that GABAergic inhibitory neurons key players cortical state modulation,

Язык: Английский

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Technical and biological sources of noise confound multiplexed enhancer AAV screening

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 16, 2025

Abstract Cis -acting regulatory enhancer elements are valuable tools for gaining cell type-specific genetic access. Leveraging large chromatin accessibility atlases, putative sequences can be identified and deployed in adeno-associated virus (AAV) delivery platforms. However, a significant bottleneck AAV discovery is charting their detailed expression patterns vivo , process that currently requires gold-standard one-by-one testing. Here we present barcoded multiplex strategy screening AAVs at type resolution using single RNA sequencing taxonomy mapping. We executed proof-of-concept study small pool of validated expressing variety neuronal non-neuronal types across the mouse brain. Unexpectedly, encountered substantial technical biological noise including chimeric packaging products, necessitating development novel techniques to accurately deconvolve patterns. These results underscore need improved methods mitigate highlight complexity biology .

Язык: Английский

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A single-cell transcriptomic atlas of developing inhibitory neurons reveals expanding and contracting modes of diversification.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 19, 2025

Abstract The cerebral cortex relies on vastly different types of inhibitory neurons to compute. How this diversity emerges during development remains an open question. rarity individual neuron often leads their underrepresentation in single-cell RNA sequencing (scRNAseq) datasets, limiting insights into developmental trajectories. To address problem, we developed a computational pipeline enrich and integrate rare cell across multiple datasets. Applying approach somatostatin-expressing (SST+) neurons—the most diverse class the cortex—we constructed Dev-SST-Atlas, comprehensive resource containing mouse transcriptomic data over 51,000 SST+ neurons. We identify three principal groups—Martinotti cells (MCs), non-Martinotti (nMCs), long-range projecting (LRPs)—each following distinct diversification MCs commit early, with embryonic neonatal clusters that map directly adult counterparts. In contrast, nMCs diversify gradually, each cluster giving rise types. LRPs follow unique ‘contracting’ mode. Initially, two are present until postnatal day 5 (P5), but by P7, one type is eliminated through programmed death, leaving single surviving population. This transient LRP also found fetal human cortex, revealing evolutionarily conserved feature cortical development. Together, these findings highlight modes diversification—invariant, expanding, contracting—offering new framework understand how large repertoire

Язык: Английский

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Vagal sensory circuits of the lower airway in respiratory physiology: Insights from neuronal diversity

Current Opinion in Neurobiology, Год журнала: 2025, Номер 92, С. 103000 - 103000

Опубликована: Март 17, 2025

Sensory neurons innervating the lower airway provide essential feedback information that regulates respiratory physiology. These synapse with second-order in central nervous system, which project directly or indirectly to and autonomic centers. Both primary sensory within these circuits exhibit significant heterogeneity, precise roles of individual neuronal subtypes coding airway's internal states modulating outputs remain incompletely understood. In this review, we summarize recent advances understanding diversity along their physiological functions. We also highlight challenges elucidating specific due extensive molecular anatomical among neurons. Improving targeting specificity for manipulation, combined development a comprehensive connectivity map, will be critical revealing wiring logics underlie control

Язык: Английский

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Enhancer AAV toolbox for accessing and perturbing striatal cell types and circuits

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 29, 2024

We present an enhancer AAV toolbox for accessing and perturbing striatal cell types circuits. Best-in-class vectors were curated major neuron populations including medium spiny neurons (MSNs), direct indirect pathway MSNs, as well Sst-Chodl, Pvalb-Pthlh, cholinergic interneurons. Specificity was evaluated by multiple modes of molecular validation, three different routes virus delivery, with diverse transgene cargos. Importantly, we provide detailed information necessary to achieve reliable type specific labeling under experimental contexts. demonstrate circuit-selective optogenetic perturbation behavior multiplex interneuron targeted analysis cellular features. Lastly, show conserved

Язык: Английский

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Adeno-associated viral tools to trace neural development and connectivity across amphibians

Developmental Cell, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 1, 2024

Язык: Английский

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Enhancer AAVs for targeting spinal motor neurons and descending motor pathways in rodents and macaque

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 31, 2024

Summary Experimental access to cell types within the mammalian spinal cord is severely limited by availability of genetic tools. To enable lower motor neurons (LMNs) and LMN subtypes, which function integrate information from brain control movement through direct innervation effector muscles, we generated single multiome datasets mouse macaque cords discovered putative enhancers for each neuronal population. We cloned these into adeno-associated viral vectors (AAVs) driving a reporter fluorophore functionally screened them in mouse. The most promising candidate were then extensively characterized using imaging molecular techniques further tested rat show conservation labeling. Additionally, combined enhancer elements vector achieve simultaneous labeling upper (UMNs) LMNs. This unprecedented toolkit will future investigations type across species potential therapeutic interventions human neurodegenerative diseases.

Язык: Английский

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The Neurobiology of Parenting and Infant-Evoked Aggression

Physiological Reviews, Год журнала: 2024, Номер 105(1), С. 315 - 381

Опубликована: Авг. 15, 2024

Parenting behavior comprises a variety of adult-infant and adult-adult interactions across multiple timescales. The state transition from nonparent to parent requires an extensive reorganization individual priorities physiology is facilitated by combinatorial hormone action on specific cell types that are integrated throughout interconnected brainwide neuronal circuits. In this review, we take comprehensive approach integrate historical current literature each these topics species, with focus rodents. New emerging molecular, circuit-based, computational technologies have recently been used address outstanding gaps in our framework knowledge infant-directed behavior. This work raising fundamental questions about the interplay between instinctive learned components parenting mutual regulation affiliative versus agonistic behaviors health disease. Whenever possible, point how helped gain novel insights opened new avenues research into neurobiology parenting. We hope review will serve as introduction for those field, resource already studying parenting, guidepost designing future studies.

Язык: Английский

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