Cardiogenic control of affective behavioural state

Nature, Journal Year: 2023, Volume and Issue: 615(7951), P. 292 - 299

Published: March 1, 2023

Abstract Emotional states influence bodily physiology, as exemplified in the top-down process by which anxiety causes faster beating of heart 1–3 . However, whether an increased rate might itself induce or fear responses is unclear 3–8 Physiological theories emotion, proposed over a century ago, have considered that general, there could be important and even dominant flow information from body to brain 9 Here, formally test this idea, we developed noninvasive optogenetic pacemaker for precise, cell-type-specific control cardiac rhythms up 900 beats per minute freely moving mice, enabled wearable micro-LED harness systemic viral delivery potent pump-like channelrhodopsin. We found optically evoked tachycardia potently enhanced anxiety-like behaviour, but crucially only risky contexts, indicating both central (brain) peripheral (body) processes may involved development emotional states. To identify potential mechanisms, used whole-brain activity screening electrophysiology find regions were activated imposed rhythms. identified posterior insular cortex mediator bottom-up interoceptive processing, inhibition region attenuated behaviour was induced optical pacing. Together, these findings reveal cells must together understand origins affective More broadly, our results define generalizable approach noninvasive, temporally precise functional investigations joint organism-wide interactions among targeted during behaviour.

Language: Английский

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An approximate line attractor in the hypothalamus encodes an aggressive state

Cell, Journal Year: 2023, Volume and Issue: 186(1), P. 178 - 193.e15

Published: Jan. 1, 2023

The hypothalamus regulates innate social behaviors, including mating and aggression. These behaviors can be evoked by optogenetic stimulation of specific neuronal subpopulations within MPOA VMHvl, respectively. Here, we perform dynamical systems modeling population activity in these nuclei during behaviors. In unsupervised analysis identified a dominant dimension neural with large time constant (>50 s), generating an approximate line attractor state space. Progression the trajectory along this was correlated escalation agonistic behavior, suggesting that it may encode scalable aggressiveness. Consistent this, individual differences magnitude integration were strongly contrast, attractors not observed mating; instead, neurons fast dynamics tuned to actions. Thus, different hypothalamic employ distinct codes represent similar

Language: Английский

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Multiregion neuronal activity: the forest and the trees

Nature reviews. Neuroscience, Journal Year: 2022, Volume and Issue: 23(11), P. 683 - 704

Published: Oct. 3, 2022

Language: Английский

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Understanding the habenula: A major node in circuits regulating emotion and motivation

Pharmacological Research, Journal Year: 2023, Volume and Issue: 190, P. 106734 - 106734

Published: March 16, 2023

Over the last decade, understanding of habenula has rapidly advanced from being an understudied brain area with Latin name 'habena" meaning "little rein", to considered a "major rein" in control key monoaminergic centers. This ancient structure is strategic node information flow fronto-limbic areas brainstem nuclei. As such, it plays crucial role regulating emotional, motivational, and cognitive behaviors been implicated several neuropsychiatric disorders, including depression addiction. review will summarize recent findings on medial (MHb) lateral (LHb) habenula, their topographical projections, cell types, functions. Additionally, we discuss contemporary efforts that have uncovered novel molecular pathways synaptic mechanisms focus MHb-Interpeduncular nucleus (IPN) synapses. Finally, explore potential interplay between habenula's cholinergic non-cholinergic components coordinating related emotional motivational behaviors, raising possibility these two work together provide balanced roles reward prediction aversion, rather than functioning independently.

Language: Английский

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Structural basis for ion selectivity in potassium-selective channelrhodopsins

Cell, Journal Year: 2023, Volume and Issue: 186(20), P. 4325 - 4344.e26

Published: Aug. 30, 2023

KCR channelrhodopsins (K

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Behavioral strategy shapes activation of the Vip-Sst disinhibitory circuit in visual cortex

Neuron, Journal Year: 2024, Volume and Issue: 112(11), P. 1876 - 1890.e4

Published: March 5, 2024

In complex environments, animals can adopt diverse strategies to find rewards. How distinct differentially engage brain circuits is not well understood. Here, we investigate this question, focusing on the cortical Vip-Sst disinhibitory circuit between vasoactive intestinal peptide-postive (Vip) interneurons and somatostatin-positive (Sst) interneurons. We characterize behavioral used by mice during a visual change detection task. Using dynamic logistic regression model, that individual use mixtures of comparison strategy statistical timing strategy. Separately, also have periods task engagement disengagement. Two-photon calcium imaging shows large strategy-dependent differences in neural activity excitatory, Sst inhibitory, Vip inhibitory cells response both image changes omissions. contrast, has limited effects population activity. diversity correlates be understood parsimoniously as increased activation strategy, which facilitates task-appropriate responses.

Language: Английский

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A line attractor encoding a persistent internal state requires neuropeptide signaling

Cell, Journal Year: 2024, Volume and Issue: 187(21), P. 5998 - 6015.e18

Published: Aug. 26, 2024

Language: Английский

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The neural pathway from the superior subpart of the medial habenula to the interpeduncular nucleus suppresses anxiety

Molecular Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

The medial habenula (MHb) and its projection target, the interpeduncular nucleus (IPN), are highly conserved throughout vertebrate evolution. MHb-IPN pathway connects limbic system to brainstem, consisting of subpathways that project in a topographically organized manner, has been implicated regulation fear anxiety. Previous studies have revealed subregion-specific functions cholinergic ventral MHb substance P (SP)-positive (SP+) subpart dorsal (dMHb). In contrast, dMHb also contains another subpart, SP-negative known as 'superior part (MHbS)'. Although MHbS characterized from various aspects, e.g. distinct c-Fos responses stressful events electrophysiological properties compared other subregions, many physiological remain be investigated. Here we found dopamine receptor D3 (DRD3)-Cre mice enable labeling IPN subregion receives projection. Cre-expressing somata within lateral subnucleus (LIPN) were concentrated most area, which refer 'lateral LIPN (lLIPN)'. This region is by absence SP+ axons, contrast (mLIPN) innervated axons MHb. Chemogenetic activation genetically induced synaptic silencing DRD3-Cre+ cells reduced enhanced anxiety-like behavior, respectively. Moreover, expression was increased lLIPN under an anxiogenic environment. These findings suggest MHbS-lLIPN activated environments counteract

Language: Английский

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GABA _B receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(8)

Published: Feb. 12, 2024

GABA B receptor (GBR) activation inhibits neurotransmitter release in axon terminals the brain, except medial habenula (MHb) terminals, which show robust potentiation. However, mechanisms underlying this enigmatic potentiation remain elusive. Here, we report that GBR on MHb induces an activity-dependent transition from a facilitating, tonic to depressing, phasic mode. This is accompanied by 4.1-fold increase readily releasable vesicle pool (RRP) size and 3.5-fold of docked synaptic vesicles (SVs) at presynaptic active zone (AZ). Strikingly, depressing exhibits looser coupling distance than release. Furthermore, are selectively affected deletion synaptoporin (SPO) Ca 2+ -dependent activator protein for secretion 2 (CAPS2), respectively. SPO modulates augmentation, short-term plasticity associated with release, CAPS2 retains increased RRP initial responses response trains. The cytosolic showed SV-associated distribution similar vesicular transmembrane SPO, they were colocalized same terminals. We developed “Flash Freeze-fracture” method, revealed SPO-associated both modes recruitment AZ during lasted several minutes. Overall, these results indicate translocates along fusion CAPS2-associated SVs, contributing persistency increase. Thus, identified structural molecular their

Language: Английский

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The lateral habenula: A hub for value-guided behavior

Cell Reports, Journal Year: 2024, Volume and Issue: 43(4), P. 113968 - 113968

Published: March 22, 2024

SummaryThe habenula is an evolutionarily highly conserved diencephalic brain region divided into two major parts, medial and lateral. Over the past decades, studies of lateral (LHb), in particular, have identified key functions value-guided behavior health disease. In this review, we focus on recent insights LHb connectivity its functional relevance for different types aversive appetitive behavior. First, give overview anatomical organization main cellular composition. Next, elaborate how distinct neuronal subpopulations encode stimuli their involvement more complex decision-making processes. Finally, scrutinize afferent efferent connections discuss implications LHb-dependent A deepened understanding circuit components will substantially contribute to our knowledge

Language: Английский

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