Molecular, spatial, and functional single-cell profiling of the hypothalamic preoptic region

Science, Год журнала: 2018, Номер 362(6416)

Опубликована: Ноя. 1, 2018

Mapping the brain, one neuron at a time Spatial transcriptomics can link molecularly described cell types to their anatomical positions and functional roles. Moffitt et al. used combination of single-cell RNA-sequencing MERFISH (multiplexed error-robust fluorescence in situ hybridization) map identity location specific within mouse preoptic hypothalamus surrounding areas brain (see Perspective by Tasic Nicovich). They related these behaviors via gene activity. The approach provides an unbiased description area, which are important for sleep, thermoregulation, thirst, social behavior. Science , this issue p. eaau5324 ; see also 749

Язык: Английский

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Social determinants of health and survival in humans and other animals

Science, Год журнала: 2020, Номер 368(6493)

Опубликована: Май 21, 2020

Social animals need connection Much research over the past decade or so has revealed that health and lifespan in humans, highly social animals, are reduced with adversity. We humans not only social, however, similar shown other mammals similarly influenced by isolation Snyder-Mackler et al. reviewed relationships between environment many aspects of well-being across nonhuman investigated similarities these patterns humans. They found same threats responses mammals. Science , this issue p. eaax9553

Язык: Английский

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Systemic AAV vectors for widespread and targeted gene delivery in rodents

Nature Protocols, Год журнала: 2019, Номер 14(2), С. 379 - 414

Опубликована: Янв. 8, 2019

Язык: Английский

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AAV capsid variants with brain-wide transgene expression and decreased liver targeting after intravenous delivery in mouse and marmoset

Nature Neuroscience, Год журнала: 2021, Номер 25(1), С. 106 - 115

Опубликована: Дек. 9, 2021

Язык: Английский

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Aversive state processing in the posterior insular cortex

Nature Neuroscience, Год журнала: 2019, Номер 22(9), С. 1424 - 1437

Опубликована: Авг. 27, 2019

Язык: Английский

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Neural mechanisms of social homeostasis

Annals of the New York Academy of Sciences, Год журнала: 2019, Номер 1457(1), С. 5 - 25

Опубликована: Март 15, 2019

Social connections are vital to survival throughout the animal kingdom and dynamic across life span. There debilitating consequences of social isolation loneliness, support is increasingly a primary consideration in health care, disease prevention, recovery. Considering connection as an "innate need," it hypothesized that evolutionarily conserved neural systems underlie maintenance connections: alerting individual their absence coordinating effector mechanisms restore contact. This reminiscent homeostatic system designed maintain connection. Here, we explore identity regulating "social homeostasis." We review findings from rodent studies evaluating rapid response deficit (in form acute isolation) propose parallel, overlapping circuits engaged adapt vulnerabilities By considering other needs, such energy fluid balance, discuss potential attributes circuitry. reason uncovering these circuits/mechanisms will facilitate our understanding how loneliness perpetuates long-term states, which speculate may result sustained recruitment circuits.

Язык: Английский

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Substance P and pain chronicity

Cell and Tissue Research, Год журнала: 2018, Номер 375(1), С. 227 - 241

Опубликована: Окт. 3, 2018

Substance P (SP) is a highly conserved member of the tachykinin peptide family that widely expressed throughout animal kingdom. The numerous members are involved in multitude neuronal signaling pathways, mediating sensations and emotional responses (Steinhoff et al. Physiol Rev 94:265–301, 2014). In contrast to receptors for classical transmitters, such as glutamate (Parsons Handb Exp Pharmacol 249–303, 2005), only minority neurons certain brain areas express neurokinin (NKRs) (Mantyh J Clin Psychiatry 63:6–10, 2002). SP also by variety non-neuronal cell types microglia, well immune cells (Mashaghi Cell Mol Life Sci 73:4249–4264, 2016). an 11-amino acid neuropeptide preferentially activates neurokinin-1 receptor (NK1R). It transmits nociceptive signals via primary afferent fibers spinal brainstem second-order (Cao Nature 392:390–394, 1998). Compounds inhibit SP's action being investigated potential drugs relieve pain. More recently, NKR have gained attention their role complex psychiatric processes. key goal field pain research understand mechanisms transition between acute chronic influence cognitive inputs feedbacks from different makes not perception but experience (Zieglgänsberger CNS Spectr 10:298–308, 2005; Trenkwaldner Sleep Med 31:78–85, 2017). This review focuses on functional plasticity dorsal horn major relay information.

Язык: Английский

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Cognitive Control of Escape Behaviour

Trends in Cognitive Sciences, Год журнала: 2019, Номер 23(4), С. 334 - 348

Опубликована: Март 6, 2019

Escape behaviours are not only simple stimulus-reactions but under cognitive control, allowing the study of processes such as decision-making and action selection in tractable organisms ethological settings. Successful escape relies on integrating multiple external internal variables, for computing flight trajectories towards shelter, implementing trade-offs by choosing between actions that satisfy competing motivations. Some neural mechanisms innate conserved across species, subject to control modification systems, including neocortex, which allow experience be flexibly incorporated into behaviour. New tools quantify behaviour while recording activity enable analysis ethologically-relevant complex environments, will advance our understanding basis natural behaviours. When faced with potential predators, animals instinctively decide whether there is a threat they should from, also when, how, where take evasive action. While often viewed classical ethology an released upon presentation specific stimuli, successful adaptive information from sensory stored knowledge, states. From neuroscience perspective, incredibly rich model provides opportunities investigating perceptual value-based decision-making, or selection, setting. We review recent research laboratory field studies explore, at behavioural mechanistic levels, how elements streams integrated generate flexible (see Glossary) instinctive defensive has evolved avoid harm predators other threats environment. Animals fail imminent suffer reduced fitness, catastrophically case death, injury, example owing ability forage food weakening social status [1Lima S.L. Dill L.M. Behavioral decisions made risk predation: prospectus.Can. J. Zool. 1990; 68: 619-640Crossref Google Scholar]. 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Eller M.C. Spatial cognition gerbil: optimal routes visual threats.Anim. Cogn. 2009; 12: 333-345Crossref (9) In addition, most important components economic because foraging patch incurs loss resources account optimizing fitness long term [7Ydenberg R.C. economics fleeing predators.Adv. Study Behav. 1986; 16: 229-249Crossref (784) 8Sih A. Prey uncertainty balancing antipredator feeding needs.Am. Nat. 1992; 139: 1052-1069Crossref (0) computation therefore integrates various streams, creates flexibility necessary survive dynamic produce escapes minimize reaction time response threats, maximize success considering much possible. This extracted encounter (e.g., current state environment), derive prior expectation about outcome action), arise signals animal, hunger anxiety. robustly trigger stimulus-dependent manner, together conditions levels complexity, make powerful systems cognition. 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Язык: Английский

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Optogenetic stimulation of medial prefrontal cortex Drd1 neurons produces rapid and long-lasting antidepressant effects

Nature Communications, Год журнала: 2019, Номер 10(1)

Опубликована: Янв. 9, 2019

Impaired function in the medial prefrontal cortex (mPFC) contributes to depression, and therapeutic response produced by novel rapid-acting antidepressants such as ketamine are mediated mPFC activity. The contains multiple types of pyramidal cells, but it is unclear whether a particular subtype mediates rapid antidepressant actions ketamine. Here we tested two major subtypes, Drd1 Drd2 dopamine receptor expressing neurons found that activating cells produces long-lasting anxiolytic responses. In contrast, photostimulation was ineffective across anxiety-like depression-like measures. Disruption activity also blocked effects Finally, demonstrate stimulation terminals BLA recapitulates somatic stimulation. These findings aid understanding cellular target downstream circuitry involved

Язык: Английский

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Delivering genes across the blood-brain barrier: LY6A, a novel cellular receptor for AAV-PHP.B capsids

PLoS ONE, Год журнала: 2019, Номер 14(11), С. e0225206 - e0225206

Опубликована: Ноя. 14, 2019

The engineered AAV-PHP.B family of adeno-associated virus efficiently delivers genes throughout the mouse central nervous system. To guide their application across disease models, and to inspire development translational gene therapy vectors for targeting neurological diseases in humans, we sought elucidate host factors responsible CNS tropism vectors. Leveraging differences 13 strains, systematically determined a set genetic variants that segregate with permissivity phenotype, rapidly identified LY6A as an essential receptor Interfering by CRISPR/Cas9-mediated Ly6a disruption or blocking antibodies reduced transduction brain endothelial cells AAV-PHP.eB, while ectopic expression increased AAV-PHP.eB HEK293T CHO 30-fold more. Importantly, demonstrate this newly discovered mode AAV binding can occur independently other known receptors. These findings illuminate previously reported species- strain-specific characteristics inform ongoing efforts develop next-generation vehicles human therapy.

Язык: Английский

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