Central amygdala circuits in valence and salience processing

Kong, Mi-Seon; Zweifel, Larry S.

doi:10.1016/j.bbr.2021.113355

Cited by 34 publications

(34 citation statements)

References 133 publications

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“…Our study adds to a growing body of literature defining the CeA as a vital limbic brain structure that integrates complex sensory information to generate survival behaviour. 23,[31][32][33] It is hypothesized that CeM output neurons control freezing through projections to the PAG, 28,34 and our results demonstrate for the first time that the CeM is also important for flight. DP-to-CeA projections target specific classes of CeM neurons that project to flight centres in the PAG, with little innervation of neuronal classes linked to freezing.…”

Section: Discussionsupporting

confidence: 54%

Top-down control of flight by a non-canonical cortico-amygdala pathway

Borkar

Stelly

et al. 2022

Preprint

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Survival requires the selection of appropriate behaviour in response to threats, and dysregulated defensive reactions are associated with psychiatric illnesses such as posttraumatic stress and panic disorder.1 Threat-induced behaviour, including panic-like flight, is controlled by neuronal circuits in the central amygdala (CeA)2; however, the source of neuronal excitation to the CeA that contributes to these high-intensity defensive responses is unknown. Here we used a combination of neuroanatomical mapping, in-vivo calcium imaging, functional manipulations, and slice physiology to characterize a previously unknown projection from the dorsal peduncular (DP) prefrontal cortex to the CeA. DP-to-CeA neurons are glutamatergic and specifically target the medial CeA. Using a behavioural paradigm that elicits both freezing and flight, we found that CeA-projecting DP neurons are activated by high-intensity threats in a context-dependent manner. Functional manipulations revealed that the DP-to-CeA pathway is necessary for both avoidance behaviour and flight. Furthermore, we found that DP projections preferentially target distinct medial CeA neuronal populations linked to flight. These results are the first demonstration that the prefrontal cortex exerts direct, top-down control of the CeA and elucidate a non-canonical pathway regulating panic-like fear responses.

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Section: Discussionsupporting

confidence: 54%

Top-down control of flight by a non-canonical cortico-amygdala pathway

Borkar

Stelly

et al. 2022

Preprint

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“…Another recent study showed that a subpopulation of PKCδ neurons that expresses Cartpt drive drinking in yohimbine stressed animals [ 19 ]. PKCδ neurons are associated with negatively valenced stimuli and fear learning [ 5 , 50 ]. They consistently respond to aversive events and assign a negative valence to conditioned stimuli in a fear learning procedure [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

“…PKCδ neurons are associated with negatively valenced stimuli and fear learning [ 5 , 50 ]. They consistently respond to aversive events and assign a negative valence to conditioned stimuli in a fear learning procedure [ 5 ]. This may indicate that PKCδ neurons drive negative emotional states associated with withdrawal, and that they may support negatively reinforcing aspects of alcohol dependence.…”

Section: Discussionmentioning

confidence: 99%

“…These GABAergic subtypes have been classified by the expression of unique marker genes, such as the peptide neurotransmitters that they release, or the various receptors and kinases that they express [1,3,4]. Within the CeA, these neurons form complex reciprocating microcircuits that control emotional behaviors, including stress responses, food seeking, and the consumption of addictive drugs [5][6][7]. CeA GABAergic subtypes can have opposing effects on these behaviors [5,[8][9][10], which necessitates studying the region at a cellular level.…”

Section: Introductionmentioning

confidence: 99%

“…Within the CeA, these neurons form complex reciprocating microcircuits that control emotional behaviors, including stress responses, food seeking, and the consumption of addictive drugs [5][6][7]. CeA GABAergic subtypes can have opposing effects on these behaviors [5,[8][9][10], which necessitates studying the region at a cellular level.…”

Section: Introductionmentioning

confidence: 99%

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Cell-type specific changes in PKC-delta neurons of the central amygdala during alcohol withdrawal

et al. 2022

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The central amygdala (CeA) contains a diverse population of cells, including multiple subtypes of GABAergic neurons, along with glia and epithelial cells. Specific CeA cell types have been shown to affect alcohol consumption in animal models of dependence and may be involved in negative affect during alcohol withdrawal. We used single-nuclei RNA sequencing to determine cell-type specificity of differential gene expression in the CeA induced by alcohol withdrawal. Cells within the CeA were classified using unbiased clustering analyses and identified based on the expression of known marker genes. Differential gene expression analysis was performed on each identified CeA cell-type. It revealed differential gene expression in astrocytes and GABAergic neurons associated with alcohol withdrawal. GABAergic neurons were further subclassified into 13 clusters of cells. Analyzing transcriptomic responses in these subclusters revealed that alcohol exposure induced multiple differentially expressed genes in one subtype of CeA GABAergic neurons, the protein kinase C delta (PKCδ) expressing neurons. These results suggest that PKCδ neurons in the CeA may be uniquely sensitive to the effects of alcohol exposure and identify a novel population of cells in CeA associated with alcohol withdrawal.

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Corticotropin‐releasing factor‐dopamine interactions in male and female macaque: Beyond the classic VTA

Kelly,

Love,

Fudge

2023

Synapse

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Dopamine (DA) is involved in stress and stress‐related illnesses, including many psychiatric disorders. Corticotropin‐releasing factor (CRF) plays a role in stress responses and targets the ventral midbrain DA system, which is composed of DA and non‐DA cells, and divided into specific subregions. Although CRF inputs to the midline A10 nuclei (“classic VTA”) are known, in monkeys, CRF‐containing terminals are also highly enriched in the expanded A10 parabrachial pigmented nucleus (PBP) and in the A8 retrorubral field subregions. We characterized CRF‐labeled synaptic terminals on DA (tyrosine hydroxylase, TH+) and non‐DA (TH–) cell types in the PBP and A8 regions using immunoreactive electron microscopy (EM) in male and female macaques. CRF labeling was present mostly in axon terminals, which mainly contacted TH‐negative dendrites in both subregions. Most CRF‐positive terminals had symmetric profiles. In both PBP and A8, CRF symmetric (putative inhibitory) synapses onto TH‐negative dendrites were significantly greater than asymmetric (putative excitatory) profiles. This overall pattern was similar in males and females, despite shifts in the size of these effects between regions depending on sex. Because stress and gonadal hormone shifts can influence CRF expression, we also did hormonal assays over a 6‐month time period and found little variability in basal cortisol across similarly housed animals at the same age. Together our findings suggest that at baseline, CRF‐positive synaptic terminals in the primate PBP and A8 are poised to regulate DA indirectly through synaptic contacts onto non‐DA neurons.

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Central amygdala circuits in valence and salience processing

Cited by 34 publications

References 133 publications

Top-down control of flight by a non-canonical cortico-amygdala pathway

Top-down control of flight by a non-canonical cortico-amygdala pathway

Cell-type specific changes in PKC-delta neurons of the central amygdala during alcohol withdrawal

Corticotropin‐releasing factor‐dopamine interactions in male and female macaque: Beyond the classic VTA

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