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| Open AccessNuclei-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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| Open AccessSocial 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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| Open AccessThe 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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| Open AccessVentromedial 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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| Open AccessA 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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| Open AccessmiR-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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| Open AccessEnvironmental 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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| Open AccessTopographic 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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| Open AccessAversive 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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| Open AccessReward 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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| Open AccessInfralimbic 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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Article
| Open AccessMapping 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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| Open AccessGq 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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| Open AccessCentral 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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| Open AccessSex differences in fear memory consolidation via Tac2 signaling in mice
The Tachykinin 2 (Tac2) pathway in the central amygdala is sufficient and necessary for modulating fear memory consolidation. The authors show that silencing Tac2 neurons in the amygdala of male mice reduces fear expression, while fear expression in female mice is increased when manipulations are made during proestrus.
- A. Florido
- , E. R. Velasco
- & R. Andero
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| Open AccessSingle cell plasticity and population coding stability in auditory thalamus upon associative learning
How thalamic sensory relays participate in plasticity upon associative fear learning and stable long-term sensory coding remains unknown. The authors show that auditory thalamus neurons exhibit heterogeneous plasticity patterns after learning while population level encoding of auditory stimuli remains stable across days.
- James Alexander Taylor
- , Masashi Hasegawa
- & Jan Gründemann
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| Open AccessGenome-wide translational profiling of amygdala Crh-expressing neurons reveals role for CREB in fear extinction learning
Fear and fear extinction learning are dynamic. These dynamic changes are underlined by transcriptional changes. Here, the authors translationally profiled Crh neurons in the amygdala and and identified relevant gene networks.
- Kenneth M. McCullough
- , Chris Chatzinakos
- & Kerry J. Ressler
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| Open AccessContextual fear memory retrieval by correlated ensembles of ventral CA1 neurons
The vCA1-BA projection is enriched in shock responsive neurons, which are necessary for fear memory encoding and become correlated with a network of neurons during retrieval. Here the authors show that the magnitude of vCA1 correlated activity is proportional to memory strength and requires the shock response during encoding.
- Jessica C. Jimenez
- , Jack E. Berry
- & Rene Hen
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| Open AccessClosed-loop control of gamma oscillations in the amygdala demonstrates their role in spatial memory consolidation
Gamma oscillations have been proposed to underlie many cognitive and memory processes, but it has proven difficult to directly test this by manipulating them. Here, in rats, the authors show that manipulation of gamma oscillations in the amygdala affects memory consolidation.
- Vasiliki Kanta
- , Denis Pare
- & Drew B. Headley
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| Open AccessLong time-scales in primate amygdala neurons support aversive learning
During learning of an association between a neutral cue and an aversive stimulus, there is a time lag between trials. Here, the authors examine how long inter-trial intervals are represented by the basolateral amygdala and anterior cingulate cortex to support learning rate and memory strength.
- Aryeh H. Taub
- , Yosef Shohat
- & Rony Paz
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| Open AccessAnterior cingulate cortex and its input to the basolateral amygdala control innate fear response
Brain circuits that control innate fear response are essential for an animal’s survival. Here, the authors report how the anterior cingulate cortex and its projection to amygdala control the innate fear response in mice.
- Jinho Jhang
- , Hyoeun Lee
- & Jin-Hee Han
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| Open AccessA dopaminergic switch for fear to safety transitions
Fear memories are overcome only when it is ascertained that fearful responses are not appropriate. Here the authors demonstrate that activity in dopamine neurons is necessary to extinguish fear responses and two distinct dopamine neuron projections exert opposing effects on extinction learning.
- Ray Luo
- , Akira Uematsu
- & Joshua P. Johansen
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| Open AccessA neuronal basis for fear discrimination in the lateral amygdala
When perceiving new stimuli, organisms need to distinguish between threats versus harmless stimuli. Here, the authors find a set of cells in the lateral amygdala that is required to discriminate or generalize new auditory stimuli based on similarity to previously fear-associate sounds.
- Anna Grosso
- , Giulia Santoni
- & Benedetto Sacchetti
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| Open AccessOrexin modulates behavioral fear expression through the locus coeruleus
Vigilance involves the activation of orexinergic neurons in the lateral hypothalamus (LH-ox). Here the authors report the functional role of a monosynaptically connected circuit with orexinergic neurons connected to noradrenergic neurons in the locus coeruleus which target lateral amygdala neurons and enhance fear expression and generalization.
- Shingo Soya
- , Tohru M. Takahashi
- & Takeshi Sakurai
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Article
| Open AccessNrp2 is sufficient to instruct circuit formation of mitral-cells to mediate odour-induced attractive social responses
Neuropilin 2 (Nrp2) is expressed by a subset of mitral cells in the postero-ventral olfactory bulb in mice. Here the authors show that Nrp2 is sufficient to instruct mitral cell targeting to the anterior part of medial amygdala that modulates olfactory-driven attractive social behaviour.
- Kasumi Inokuchi
- , Fumiaki Imamura
- & Hitoshi Sakano
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| Open AccessEndogenous opioids regulate social threat learning in humans
Though humans often learn about negative outcomes from observing the response of others, the neurochemistry underlying this learning is unknown. Here, authors show that blocking opioid receptors enhances social threat learning and describe the brain regions underlying this effect.
- Jan Haaker
- , Jonathan Yi
- & Andreas Olsson
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| Open AccessThe human amygdala parametrically encodes the intensity of specific facial emotions and their categorical ambiguity
The amygdala processes emotional facial expressions, but its exact contributions are unclear. Wang.et al. use behavioural analysis of amygdala lesion patients, fMRI, and single-neuron recordings to show that both emotional intensity and ambiguity signals are processed in the human amygdala.
- Shuo Wang
- , Rongjun Yu
- & Ueli Rutishauser
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| Open AccessA retinoraphe projection regulates serotonergic activity and looming-evoked defensive behaviour
Neural circuits underlying innate fear are only partially understood. Huanget al. identify a subset of retinal ganglion cells that project to both the dorsal raphe nucleus and the superior colliculus, and show that these RGCs mediate looming-evoked defensive behaviours in mice.
- Lu Huang
- , Tifei Yuan
- & Chaoran Ren
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| Open AccessAmygdala-hippocampal dynamics during salient information processing
Amygdala and hippocampus are involved in processing motivationally salient stimuli but the precise circuit dynamics of the interaction is not understood. Here the authors show that in response to fearful faces in humans, theta/alpha oscillations in the amygdala modulate hippocampal activity dynamics.
- Jie Zheng
- , Kristopher L. Anderson
- & Jack J. Lin
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Article
| Open AccessNeural correlates of two different types of extinction learning in the amygdala central nucleus
There are two forms of extinction learning, which are vital for adaptive behaviour: simple extinction, when an expected outcome fails to occur, and overexpectation, when an exaggerated expectation is in conflict with the actual outcome. Iordanova et al.show that both forms of extinction learning have a common neural substrate in the amygdala.
- Mihaela D. Iordanova
- , Mickael L. D. Deroche
- & Geoffrey Schoenbaum
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| Open AccessBasolateral amygdala nucleus responses to appetitive conditioned stimuli correlate with variations in conditioned behaviour
Neurons in the basolateral amygdala show increased response to conditioned stimuli predicting rewards. Here the authors show that their activity is not correlated with the reward-predicting stimulus but rather with the conditioned behaviour.
- Seung-Chan Lee
- , Alon Amir
- & Denis Pare
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Article
| Open AccessOpposite monosynaptic scaling of BLP–vCA1 inputs governs hopefulness- and helplessness-modulated spatial learning and memory
How emotions affect memory is an open question. Here the authors establish learnt hopeful and learnt helpless mouse models, and find that posterior basolateral amygdala to ventral hippocampal CA1 monosynaptic glutamatergic inputs link emotions to spatial memory performance.
- Ying Yang
- , Zhi-Hao Wang
- & Jian-Zhi Wang
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Article
| Open AccessEphrin-B3 coordinates timed axon targeting and amygdala spinogenesis for innate fear behaviour
The molecular mechanism underlying initial circuit wiring in amygdala is poorly understood. Here the authors show that ephrin-B3 is required for axon targeting and amygdala spinogenesis during a critical period in development, and plays an important role in amygdala mediated fear responses.
- Xiao-Na Zhu
- , Xian-Dong Liu
- & Nan-Jie Xu
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| Open AccessBasolateral and central amygdala differentially recruit and maintain dorsolateral striatum-dependent cocaine-seeking habits
Drug seeking behaviour has habitual neural substrates. Here, Murray et al. show that the basolateral amygdala and central nucleus of the amygdala are necessary to recruit and maintain, respectively, the intrastriatal functional transition that underlies cocaine seeking habits.
- Jennifer E. Murray
- , Aude Belin-Rauscent
- & David Belin
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| Open AccessAmygdala lesions in rhesus macaques decrease attention to threat
The amygdala in the medial temporal lobe of the human and non-human primate brain is known to process salient social stimuli and to mediate threat discrimination. Here, Dal Monte et al.show that rhesus monkeys with amygdala lesions have deficits in detecting threat signals and directing attention to the eye region of a conspecific's face.
- Olga Dal Monte
- , Vincent D. Costa
- & Bruno B. Averbeck
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| Open AccessProcessing of visually evoked innate fear by a non-canonical thalamic pathway
The ability of animals to respond to life-threatening stimuli is critical for survival, yet the neural circuits mediating innate defensive behaviors are not well understood. Here, the authors reveal a novel collicular–thalamic–amygdala circuit critical for innate defensive responses to visual threats.
- Pengfei Wei
- , Nan Liu
- & Liping Wang
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FAAH genetic variation enhances fronto-amygdala function in mouse and human
Fatty acid amide hydrolase (FAAH) is a key regulator of endocannabinoid signalling. Here, the authors develop a knock-in mouse that recapitulates a common human mutation in the FAAH gene and demonstrate parallel neural and behavioural alterations across species, suggesting a gain-of-function in fear regulation.
- Iva Dincheva
- , Andrew T. Drysdale
- & Francis S. Lee
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Prefrontal cortex reactivity underlies trait vulnerability to chronic social defeat stress
Connectivity between the prefrontal cortex (PFC) and the amygdala (AMY) is implicated in responses to stress and regulation of affect. Here, the authors show that stress is regulated by changes in PFC–AMY coherence, PFC oscillatory activity and AMY oscillatory activity across the 2–7 Hz frequency band.
- Sunil Kumar
- , Rainbo Hultman
- & Kafui Dzirasa
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Identity of endogenous NMDAR glycine site agonist in amygdala is determined by synaptic activity level
NMDA receptor activation requires the occupation of binding sites by glutamate and a glycine site agonist. Li and colleagues study this in synapses of the lateral nucleus of the amygdala and find that the identity of the NMDAR glycine site agonist depends on the level of synaptic activation.
- Yan Li
- , Silvia Sacchi
- & Vadim Y. Bolshakov