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Synergism between two BLA-to-BNST pathways for appropriate expression of anxiety-like behaviors in male mice
How distinct circuits get coordinated to allow individuals to express appropriate level of anxiety is unclear. Here, authors show there are two functionally opposing BLA-BNST pathways interacting via the local inhibitory networks to enable anxiety expression with environmental needs.
- Ren-Wen Han
- , Zi-Yi Zhang
- & Bing-Xing Pan
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Stress increases hepatic release of lipocalin 2 which contributes to anxiety-like behavior in mice
Cross talk between periphery and the central nervous system may contribute to stress associated behaviours. Here the authors identified liver-derived lipocalin 2 as a peripheral factor that elicits anxiety-like behaviours via modulating medial prefrontal neural activity.
- Lan Yan
- , Fengzhen Yang
- & Li Zhang
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Replication study on the role of dopamine-dependent prefrontal reactivations in human extinction memory retrieval
Dopamine may help strengthen fear-inhibitory extinction memories through influences on the prefrontal cortex. Here, the authors replicate their previous finding that prefrontal reactivations are predictive of extinction memory retrieval but do not replicate the enhancing effects of L-DOPA.
- Elena Andres
- , Hu Chuan-Peng
- & Raffael Kalisch
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Serotonergic modulation of vigilance states in zebrafish and mice
To successfully escape a predator, animals usually maintain a vigilance state, the neural basis of which was unknown. Here, authors show a 5-HT driven mechanism operating at neural circuit level which shapes the vigilance state in zebrafish and mice.
- Yang Zhao
- , Chun-Xiao Huang
- & Jianren Song
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Nuclei-specific hypothalamus networks predict a dimensional marker of stress in humans
The association between connectivity of the hypothalamus and stress is not well understood. Here, the authors show connectivity between hypothalamic nuclei and other subcortical structures is predictive of stress.
- Daria E. A. Jensen
- , Klaus P. Ebmeier
- & Miriam C. Klein-Flügge
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Distributed neural representations of conditioned threat in the human brain
Discriminating threat from safety is critical for humans to navigate their environment. Here, the authors show that neural representations of threat and safety are distributed across brain systems that are robustly decoded across threat paradigms.
- Zhenfu Wen
- , Edward F. Pace-Schott
- & Mohammed R. Milad
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Social buffering in rats reduces fear by oxytocin triggering sustained changes in central amygdala neuronal activity
After rats were trained to fear a sound, they showed less fear when another rat was nearby and this calming effect lasted when the other rat was removed. Both reductions required oxytocin signaling from the hypothalamus to the central amygdala.
- Chloe Hegoburu
- , Yan Tang
- & Ron Stoop
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A neural signature for the subjective experience of threat anticipation under uncertainty
The neural systems which underlie the experience of anticipated threat under uncertainty are not well understood. Here, the authors find a whole-brain signature which specifically predicts anxious anticipation.
- Xiqin Liu
- , Guojuan Jiao
- & Benjamin Becker
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Persistent enhancement of basolateral amygdala-dorsomedial striatum synapses causes compulsive-like behaviors in mice
Compulsivity is associated with many psychiatric disorders including obsessive compulsive disorder. However, the neural circuits that mediate this trait are not clearly defined. Here the authors show that the amygdalostriatal circuit plays a critical role in the pathophysiology of compulsive-like behavior.
- In Bum Lee
- , Eugene Lee
- & Bong-June Yoon
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Awake ripples enhance emotional memory encoding in the human brain
The neural dynamics of emotional memory consolidation are not well understood. Here, the authors analyse intracranial recordings from human participants after emotional memory encoding, showing that ripple-locked activity in the amygdala and hippocampus is predictive of subsequent memory.
- Haoxin Zhang
- , Ivan Skelin
- & Jack J. Lin
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The amygdala is not necessary for the familiarity aspect of recognition memory
It has been proposed that the amygdala is required for the familiarity aspect of item recognition. By studying the performance of monkeys with selective amygdala lesions on four converging memory paradigms, the authors demonstrate that the amygdala is not necessary for familiarity memory, but confirm its role in reward processing.
- Benjamin M. Basile
- , Vincent D. Costa
- & Elisabeth A. Murray
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Ventral striatal islands of Calleja neurons bidirectionally mediate depression-like behaviors in mice
Ventral striatal Islands of Calleja neurons, known to regulate grooming in mice, are reported to bidirectionally mediate depression-like behaviors. Here, authors link grooming, dopamine signaling and affective behaviors via ventral striatal circuits.
- Yun-Feng Zhang
- , Jialiang Wu
- & Minghong Ma
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Activity-dependent organization of prefrontal hub-networks for associative learning and signal transformation
Neuronal populations in the prefrontal cortex are involved in associative learning. Here the authors use longitudinal imaging and computational approaches in the mouse prefrontal cortex to observe changes in neuronal ensembles during fear conditioning.
- Masakazu Agetsuma
- , Issei Sato
- & Takeharu Nagai
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Linking emotional valence and anxiety in a mouse insula-amygdala circuit
The existence of a common substrate for emotional valence and anxiety remained elusive. Here we show that excitatory neurons of the anterior insular cortex (aIC), including neurons projecting to the basolateral amygdala (aIC-BLA) encode both states.
- C. Nicolas
- , A. Ju
- & A. Beyeler
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Anxious individuals shift emotion control from lateral frontal pole to dorsolateral prefrontal cortex
Why anxious individuals fail to control emotional behaviour is not well understood. Here, the authors show that highly anxious individuals have a more excitable lateral frontopolar cortex, and fail to recruit this region during emotional action control.
- Bob Bramson
- , Sjoerd Meijer
- & Karin Roelofs
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The default network dominates neural responses to evolving movie stories
How brain networks process dynamic naturalistic stimuli is not well understood. Here, the authors use machine learning algorithms to show that brain states in the default network capture the semantic aspects of an unfolding narrative during movie watching.
- Enning Yang
- , Filip Milisav
- & Danilo Bzdok
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Ventromedial prefrontal neurons represent self-states shaped by vicarious fear in male mice
Observational fear is accompanied by both freezing and escape behavior in rodents. Here, the authors show that ventromedial prefrontal cortex (vmPFC) inhibition disrupts escape behavior specifically, and that vmPFC neural activity represents intermingled information of other- and self-states.
- Ziyan Huang
- , Myung Chung
- & Teruhiro Okuyama
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A pilot study of closed-loop neuromodulation for treatment-resistant post-traumatic stress disorder
Neurostimulation has been proposed as a potential approach for treatment-resistant PTSD. Here in a pilot study the authors show that amygdala theta activity is heightened during aversive and symptomatic experiences in patients with treatment-resistant post-traumatic stress disorder, and reduced following significant clinical improvement associated with closed-loop stimulation.
- Jay L. Gill
- , Julia A. Schneiders
- & Jean-Philippe Langevin
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Mesolimbic dopamine release precedes actively sought aversive stimuli in mice
Animals may approach normally aversive stimuli such as an air puff when in a non-enriched environment. Here the authors show that dopamine release in the ventral lateral striatum was reduced by aversive stimulation, but was increased when it was actively sought.
- Yosuke Yawata
- , Yu Shikano
- & Yuji Ikegaya
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miR-483-5p offsets functional and behavioural effects of stress in male mice through synapse-targeted repression of Pgap2 in the basolateral amygdala
The role of miRNAs in regulating brain stress response remains relatively unexplored. Here the authors show that miR-483-5p-mediated repression of Pgap2 in amygdala of male mice offsets the functional and behavioural consequences of stress.
- Mariusz Mucha
- , Anna E. Skrzypiec
- & Robert Pawlak
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Environmental context-dependent activation of dopamine neurons via putative amygdala-nigra pathway in macaques
How the primate dopamine system retains information on higher-order factors such as environmental context remains elusive. Here, the authors show tonic activity changes of dopamine neurons in different environments and the involvement of a putative amygdala-nigra pathway in such neural modulation.
- Kazutaka Maeda
- , Ken-ichi Inoue
- & Okihide Hikosaka
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Lateral septum adenosine A2A receptors control stress-induced depressive-like behaviors via signaling to the hypothalamus and habenula
The mechanism underlying caffeine consumption inversely correlation with depression is unclear. Here, authors identified adenosine A2A receptor in the lateral septum mediating depressive symptoms via direct outputs to the habenula and the hypothalamus.
- Muran Wang
- , Peijun Li
- & Wei Guo
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The cerebellum regulates fear extinction through thalamo-prefrontal cortex interactions in male mice
Fear extinction is a learning process controlled by the prefrontal cortex. Here, authors show that the cerebellum regulates fear extinction via projections to the medio-dorsal thalamus and the modulation of thalamo-prefrontal cortex interactions.
- Jimena L. Frontera
- , Romain W. Sala
- & Clément Léna
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Topographic representation of current and future threats in the mouse nociceptive amygdala
Adaptive behavior requires using both memories and ongoing experience. Here, the authors find that amygdala neurons topographically encode sensory stimuli including predicted versus ongoing threats to contribute to appropriate behaviors.
- Anna J. Bowen
- , Y. Waterlily Huang
- & Richard D. Palmiter
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Parabrachial-to-parasubthalamic nucleus pathway mediates fear-induced suppression of feeding in male mice
Feeding and stress are deeply related to each other, yet neural circuits how they interact are not fully understood. Here, the authors show that the parabrachial-to-parasubthalamic nucleus pathway is involved in fear-induced feeding suppression.
- Takashi Nagashima
- , Suguru Tohyama
- & Ayako M. Watabe
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The estrous cycle modulates early-life adversity effects on mouse avoidance behavior through progesterone signaling
Early-life adversity (ELA) can lead to anxiety disorders, which are more prevalent and debilitating in women than men. Here, authors reveal how ELA interacts with neurosteroid synthesis in the hippocampus to drive avoidance behavior in female mice.
- Blake J. Laham
- , Sahana S. Murthy
- & Elizabeth Gould
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A circuit from the ventral subiculum to anterior hypothalamic nucleus GABAergic neurons essential for anxiety-like behavioral avoidance
Anxiety is thought to be evolutionarily rooted in predator defense. Yan et al. show that GABAergic neurons in the anterior hypothalamic nucleus (AHN), a node in the predator defense network, play an essential role in anxiety-like behaviors.
- Jing-Jing Yan
- , Xiao-Jing Ding
- & Xiao-Hong Xu
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Hippocampal astrocytes modulate anxiety-like behavior
Astrocytes affect animal behaviors by regulating the tripartite synapse. Here, the authors show that hippocampal astrocytes modulate mouse anxiety-like behavior by regulating synaptic homeostasis of dentate gyrus granule cells via ATP release.
- Woo-Hyun Cho
- , Kyungchul Noh
- & Sung Joong Lee
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Aversive memory formation in humans involves an amygdala-hippocampus phase code
The amygdala facilitates memory encoding in the hippocampus. Here the authors show, using simultaneous intracranial recordings from these regions, that emotional memory encoding is mediated by the amygdala theta phase to which hippocampal gamma activity and neuronal firing is coupled.
- Manuela Costa
- , Diego Lozano-Soldevilla
- & Bryan A. Strange
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Layer-specific, retinotopically-diffuse modulation in human visual cortex in response to viewing emotionally expressive faces
Face stimuli that are perceived as emotionally expressive rather than neutral are associated with specific neural responses in V1. Here the authors show that valence information perceived from facial expressions is computed in the amygdala and fed back to V1 via direct anatomical projections.
- Tina T. Liu
- , Jason Z Fu
- & Elisha P. Merriam
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Reward and aversion processing by input-defined parallel nucleus accumbens circuits in mice
The nucleus accumbens (NAc) is involved in mediating reward seeking and negative valence. Here, the authors present evidence for afferent-specific circuitry of the NAc in the control of reward and aversion via two distinct pathway.
- Kuikui Zhou
- , Hua Xu
- & Yingjie Zhu
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Brainstem networks construct threat probability and prediction error from neuronal building blocks
The prevailing view of threat computation is a division of labor in which the forebrain signals threat and the brainstem organizes behavior. Using neuropixels, the authors show that brainstem neurons organize into a functional network to signal threat.
- Jasmin A. Strickland
- & Michael A. McDannald
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Infralimbic medial prefrontal cortex signalling to calbindin 1 positive neurons in posterior basolateral amygdala suppresses anxiety- and depression-like behaviours
The neural mechanisms for reward generalization are not fully understood. Here the authors investigate the role of posterior basolateral amygdala calbindin-expressing cells in modulating behavioural responses related to reward and aversion.
- Huiling Yu
- , Liping Chen
- & Jian-Zhi Wang
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Mapping effective connectivity of human amygdala subdivisions with intracranial stimulation
The amygdala is known to be engaged in emotional and autonomic function, yet the detailed functional connectivity of the human amygdala remains unclear. Here, the authors examine effective connectivity in the amygdala of patients with epilepsy using direct focal electrical stimulation.
- Masahiro Sawada
- , Ralph Adolphs
- & Hiroyuki Oya
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A functional role of meningeal lymphatics in sex difference of stress susceptibility in mice
The mechanisms underlying sex differences in response to stress are unclear. Here, the authors show that meningeal lymphatics dysfunction modulates the sex difference in the stress susceptibility to depression- and anxiety-like behaviours in mice.
- Weiping Dai
- , Mengqian Yang
- & Xiaojing Ye
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Lateral habenula glutamatergic neurons projecting to the dorsal raphe nucleus promote aggressive arousal in mice
The dorsal raphe nucleus (DRN) is known to modulate aggressive behaviour in rodents. Here the authors show that glutamatergic projections from the lateral habenula to DRN modulate aggression between male mice.
- Aki Takahashi
- , Romain Durand-de Cuttoli
- & Scott J. Russo
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Serotonin limits generation of chromaffin cells during adrenal organ development
Adrenal glands are major organs regulating stress response., Melnikova et al., show that local release of serotonin limits adrenalin-producing cell number during rodent development, a mechanism which has implications for neuroblastoma development and stress-related maternal effects transmitted to progeny.
- Polina Kameneva
- , Victoria I. Melnikova
- & Igor Adameyko
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A probabilistic map of emotional experiences during competitive social interactions
Emotions motivate decision-making but are difficult to measure. Here the authors use a data driven, machine learning approach to reveal that social choices are linked to a diverse array of emotions, including disappointment and sadness.
- Joseph Heffner
- & Oriel FeldmanHall
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Gq neuromodulation of BLA parvalbumin interneurons induces burst firing and mediates fear-associated network and behavioral state transition in mice
The authors study mechanisms underlying neuromodulatory control of transitions between brain and behavioral states. They identify a mechanism whereby modulation of Gq activity in basolateral amygdala parvalbumin interneurons mediates the transition to a fear-associated network and behavioral state.
- Xin Fu
- , Eric Teboul
- & Jeffrey G. Tasker
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A bottom-up reward pathway mediated by somatostatin neurons in the medial septum complex underlying appetitive learning
Reward behaviour such as food seeking is essential for survival. Shen et al. describe an ascending neural pathway mediating transformation of rewarding taste signals and reward-cue associative learning via somatostatin neurons in the medial septum.
- Li Shen
- , Guang-Wei Zhang
- & Huizhong W. Tao
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NAc-VTA circuit underlies emotional stress-induced anxiety-like behavior in the three-chamber vicarious social defeat stress mouse model
Using a three-chamber vicarious social defeat stress model in mice, Qi et al. show that chronic emotional stress (CES) induced anxiety-like behavior and transient social interaction changes. Bidirectional modulation of NAc-VTA circuit mimics or reverses the CES-induced anxiety-like behavior.
- Guangjian Qi
- , Pei Zhang
- & Bo Tian
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Article
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Dopamine promotes aggression in mice via ventral tegmental area to lateral septum projections
The authors show that terminal activity of dopaminergic neurons selectively projecting from the ventral tegmental area to the lateral septum is sufficient for promoting aggression and necessary for establishing baseline aggression in mice.
- Darshini Mahadevia
- , Rinki Saha
- & Mark S. Ansorge
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Article
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A distributed fMRI-based signature for the subjective experience of fear
The brain systems underlying fear experience are debated. Here the authors develop an fMRI-based neural signature for fear and show that fear is represented in distributed brain systems rather than isolated ‘fear centers’.
- Feng Zhou
- , Weihua Zhao
- & Benjamin Becker
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Article
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Finding positive meaning in memories of negative events adaptively updates memory
Finding positive meaning in past negative events is associated with enhanced mental health. Here the authors show this adaptively updates memory, leading to enhanced positive emotion and content at future retrieval, which remains two months later.
- Megan E. Speer
- , Sandra Ibrahim
- & Mauricio R. Delgado
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Article
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Ketamine increases activity of a fronto-striatal projection that regulates compulsive behavior in SAPAP3 knockout mice
Intravenous infusion of ketamine rapidly reduces obsessive-compulsive disorder symptoms. Here, the authors show in mice that ketamine acts by increasing activity in a fronto-striatal circuit that causally controls compulsive grooming behaviour.
- Gwynne L. Davis
- , Adelaide R. Minerva
- & Lisa A. Gunaydin
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Article
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The paraventricular thalamus provides a polysynaptic brake on limbic CRF neurons to sex-dependently blunt binge alcohol drinking and avoidance behavior in mice
Bed nucleus of the stria terminalis (BNST) neurons that synthesize and release the stress neuropeptide corticotropin-releasing factor drive binge alcohol drinking and anxiety. The authors describe a complex feedforward inhibitory PVTVGLUT2-BNSTCRF circuit in mice that plays sex-dependent roles in alcohol drinking and avoidance behavior.
- Olivia B. Levine
- , Mary Jane Skelly
- & Kristen E. Pleil
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Article
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Central amygdala micro-circuits mediate fear extinction
The central amygdala inhibitory microcircuits mediate fear extinction by reversible, stimulus- and context-specific changes in neuronal responses. These alterations are absent when extinction is deficient and selective silencing of PKCδ neurons impairs fear extinction.
- Nigel Whittle
- , Jonathan Fadok
- & Stéphane Ciocchi
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Article
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Ventral tegmental area GABA neurons mediate stress-induced blunted reward-seeking in mice
Acute stress transiently disrupts reward-seeking behaviour and repeated stress exposure produces lasting anhedonia-like behaviour in rodents. Here, the authors show that stress triggers GABAergic activity in the ventral tegmental area which blunts reward-seeking behaviour in mice.
- Daniel C. Lowes
- , Linda A. Chamberlin
- & Alexander Z. Harris
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Article
| Open Access
Infant gut microbiome composition is associated with non-social fear behavior in a pilot study
Experimental manipulation of the gut microbiome in animal models impacts fear behaviours. Here, the authors show in a pilot study that features of the human infant gut microbiome are associated with non-social fear behaviours during a laboratory based assessment.
- Alexander L. Carlson
- , Kai Xia
- & Rebecca C. Knickmeyer
A non-image-forming visual circuit mediates the innate fear of heights in male mice