Spatial transcriptomic analysis of the mouse brain following chronic social defeat stress DOI Creative Commons
Ting Wang, Zhihong Song, Xin Zhao

и другие.

Exploration, Год журнала: 2023, Номер 3(6)

Опубликована: Окт. 13, 2023

Depression is a highly prevalent and disabling mental disorder, involving numerous genetic changes that are associated with abnormal functions in multiple regions of the brain. However, there little transcriptomic-wide characterization chronic social defeat stress (CSDS) to comprehensively compare transcriptional brain regions. Spatial transcriptomics (ST) was used reveal spatial difference gene expression control, resilient (RES) susceptible (SUS) mouse brains, annotated eight anatomical six cell types. The profiles uncovered CSDS leads synchrony different Then it identified inhibitory neurons synaptic were primarily affected by CSDS. Hippocampus (HIP), Isocortex, Amygdala (AMY) present more pronounced genes depressive psychiatric disorders than other Signalling communication between these three may play critical role susceptibility Taken together, this study provides important new insights into at ST level, which offers approach for understanding treating depression.

Язык: Английский

Spatial transcriptomics reveal neuron–astrocyte synergy in long-term memory DOI Creative Commons
Wenfei Sun, Zhihui Liu, Xian Jiang

и другие.

Nature, Год журнала: 2024, Номер 627(8003), С. 374 - 381

Опубликована: Фев. 7, 2024

Abstract Memory encodes past experiences, thereby enabling future plans. The basolateral amygdala is a centre of salience networks that underlie emotional experiences and thus has key role in long-term fear memory formation 1 . Here we used spatial single-cell transcriptomics to illuminate the cellular molecular architecture memory. We identified transcriptional signatures subpopulations neurons astrocytes were memory-specific persisted for weeks. These implicate neuropeptide BDNF signalling, MAPK CREB activation, ubiquitination pathways, synaptic connectivity as components Notably, upon formation, neuronal subpopulation defined by increased Penk decreased Tac expression constituted most prominent component engram amygdala. changes observed both with RNA sequencing single-molecule intact slices, providing rich map engram. data enabled us determine this interacts adjacent astrocytes, functional experiments show require interactions encode

Язык: Английский

Процитировано

64
Mixed selectivity: Cellular computations for complexity DOI Creative Commons
Kay M. Tye, Earl K. Miller, Felix Taschbach

и другие.

Neuron, Год журнала: 2024, Номер 112(14), С. 2289 - 2303

Опубликована: Май 9, 2024

The property of mixed selectivity has been discussed at a computational level and offers strategy to maximize power by adding versatility the functional role each neuron. Here, we offer biologically grounded implementational-level mechanistic explanation for in neural circuits. We define pure, linear, nonlinear discuss how these response properties can be obtained simple Neurons that respond multiple, statistically independent variables display selectivity. If their activity expressed as weighted sum, then they exhibit linear selectivity; otherwise, Neural representations based on diverse are high dimensional; hence, confer enormous flexibility downstream readout circuit. However, circuit cannot possibly encode all possible mixtures simultaneously, this would require combinatorially large number neurons. Gating mechanisms like oscillations neuromodulation solve problem dynamically selecting which transmitted readout.

Язык: Английский

Процитировано

36
Anxiety and depression: A top‐down, bottom‐up model of circuit function DOI Creative Commons
Deryn O. LeDuke,

Matilde Borio,

Raymundo Miranda

и другие.

Annals of the New York Academy of Sciences, Год журнала: 2023, Номер 1525(1), С. 70 - 87

Опубликована: Май 2, 2023

Abstract A functional interplay of bottom‐up and top‐down processing allows an individual to appropriately respond the dynamic environment around them. These modalities can be represented as attractor states using a dynamical systems model brain. The transition probability move from one state another is dependent on stability, depth, neuromodulatory tone, tonic changes in plasticity. However, how does relationship between these change disease states, such anxiety or depression? We describe Marr's computational‐algorithmic‐implementation perspective understand depressive anxious states. illustrate examples basolateral amygdala signaling projections medial prefrontal cortex internal projections. Understanding dynamics help us better multifaceted elements depression.

Язык: Английский

Процитировано

29
Stress relief as a natural resilience mechanism against depression-like behaviors DOI Creative Commons
Yiyan Dong, Yifei Li, Xinkuan Xiang

и другие.

Neuron, Год журнала: 2023, Номер 111(23), С. 3789 - 3801.e6

Опубликована: Сен. 29, 2023

Relief, the appetitive state after termination of aversive stimuli, is evolutionarily conserved. Understanding behavioral role this well-conserved phenomenon and its underlying neurobiological mechanisms are open important questions. Here, we discover that magnitude relief from physical stress strongly correlates with individual resilience to depression-like behaviors in chronic stressed mice. Notably, blocking causes vulnerability behaviors, whereas natural rewards supplied shortly promotes resilience. Stress mediated by reward-related mesolimbic dopamine neurons, which show minute-long, persistent activation termination. Circuitry-wise, or inhibition circuits downstream ventral tegmental area during transient period bi-directionally regulates depression These results reveal an evolutionary function identify neural substrate mediating effect. Importantly, our data suggest a strategy augmenting positive valence prevent depression.

Язык: Английский

Процитировано

28
Emotional words evoke region- and valence-specific patterns of concurrent neuromodulator release in human thalamus and cortex DOI Creative Commons
Seth R. Batten,

Alec Hartle,

Leonardo S. Barbosa

и другие.

Cell Reports, Год журнала: 2025, Номер 44(1), С. 115162 - 115162

Опубликована: Янв. 1, 2025

Words represent a uniquely human information channel-humans use words to express thoughts and feelings assign emotional valence experience. Work from model organisms suggests that assignments are carried out in part by the neuromodulators dopamine, serotonin, norepinephrine. Here, we ask whether signaling these extends word semantics humans measuring sub-second neuromodulator dynamics thalamus (N = 13) anterior cingulate cortex 6) of individuals evaluating positive, negative, neutrally valenced words. Our combined results suggest modulate release both cortex, but with region- valence-specific response patterns, as well hemispheric dependence for dopamine cingulate. Overall, experiments provide evidence neuromodulator-dependent humans, not simple one-valence-per-transmitter fashion.

Язык: Английский

Процитировано

2
Endocannabinoids facilitate transitory reward engagement through retrograde gain control DOI Open Access
David J. Marcus,

Anthony E. English,

Ge Chun

и другие.

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

Опубликована: Янв. 7, 2025

Neuromodulatory signaling is poised to serve as a neural mechanism for gain control, acting crucial tuning factor influence neuronal activity by dynamically shaping excitatory and inhibitory fast neurotransmission. The endocannabinoid (eCB) system, the most widely expressed neuromodulatory system in mammalian brain, known filter inputs through retrograde, pre-synaptic action. However, whether eCBs exert retrograde control ultimately facilitate reward-seeking behaviors freely moving mammals not established. Using suite of vivo physiological, imaging, genetic machine learning-based approaches, we report fundamental role controlling behavioral engagement behavior defined thalamo-striatal circuit.

Язык: Английский

Процитировано

1
Dynorphin modulates reward-seeking actions through a pallido-amygdala cholinergic circuit DOI
Qingtao Sun, Mingzhe Liu, Wuqiang Guan

и другие.

Neuron, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

1
Altered neurotransmission in stress-induced depressive disorders: The underlying role of the amygdala in depression DOI
Muhammad Asim, Huajie Wang, Abdul Waris

и другие.

Neuropeptides, Год журнала: 2023, Номер 98, С. 102322 - 102322

Опубликована: Янв. 20, 2023

Язык: Английский

Процитировано

20
Neurotensin and energy balance DOI Open Access
Graydon B. Gereau, Sy’Keria Garrison, Zoé A. McElligott

и другие.

Journal of Neurochemistry, Год журнала: 2023, Номер 166(2), С. 189 - 200

Опубликована: Июнь 13, 2023

Abstract The neurotensin system spans across the central nervous system, to enteric (gut), and periphery govern behaviors physiological responses that tune energy balance maintain homeostasis. Neurotensin transmission is not only modulated by metabolic signals, itself can also impact state exerting control over consumption, physical activity, satiety signals. Many sensory experiences sleep processes are dictated neurotensinergic activity via mechanisms allow organism seeking utilization thrive in its environment. Given broad reach signaling has homeostatic landscape, understanding this as a whole examining new ways target for therapeutic efficacy many different conditions necessary. image

Язык: Английский

Процитировано

20
Neurotensin and Neurotensin Receptors in Stress-related Disorders: Pathophysiology & Novel Drug Targets DOI
Grigorios Kyriatzis, Michel Khrestchatisky, Lotfi Ferhat

и другие.

Current Neuropharmacology, Год журнала: 2023, Номер 22(5), С. 916 - 934

Опубликована: Авг. 3, 2023

Neurotensin (NT) is a 13-amino acid neuropeptide widely distributed in the CNS that has been involved pathophysiology of many neural and psychiatric disorders. There are three known neurotensin receptors (NTSRs), which mediate multiple actions, form neurotensinergic system conjunction with NT. NTSR1 main mediator NT, displaying effects both periphery, while NTSR2 mainly expressed brain NTSR3 broader expression pattern. In this review, we bring together up-to-date studies showing an involvement different aspects stress response stress-related disorders, such as depression anxiety, post-traumatic disorder (PTSD) its associated symptoms, fear memory maternal separation, ethanol addiction, substance abuse. Emphasis put on gene, mRNA, protein alterations NT NTSRs, well behavioral pharmacological studies, leading to evidence-based suggestions implicated regulating mechanisms their therapeutic exploitation. Stress responses anxiety involve NTSR1, but also NTSR3. primarily depression, secondarily PTSD. interrelated drug abuse memory, all NTSRs seem be consumption. Some actions these pathological settings may driven through interactions between corticotrophin releasing factor (CRF) regulatory contribution, by NT's pro-inflammatory mediating actions.

Язык: Английский

Процитировано

19