Central amygdala PKC-δ+ neurons mediate the influence of multiple anorexigenic signals

Cai, Haijiang; Haubensak, Wulf; Anthony, Todd E.; Anderson, David J.

doi:10.1038/nn.3767

Cited by 321 publications

(368 citation statements)

References 49 publications

Supporting

Mentioning

350

Contrasting

Order By: Relevance

“…We also labelled other CeAl-specific genetic markers, such as SOM, and Tackykinin 2 (Tac2) by genetic labelling, and PKC-δ with immunohistochemical staining. Immunolabelled PKC-δ virtually recapitulates what is observed with its genetic labeling (Cai et al, 2014), allowing for its comparison with knock-in tdTomato reporters. These genetic markers were all expressed in the CeAl, but the number of labelled neurons and their spatial distribution were different for each marker (Figure 5).…”

Section: Resultsmentioning

confidence: 75%

Elucidating an Affective Pain Circuit that Creates a Threat Memory

Han

Soleiman

Soden

et al. 2015

Cell

358

450

View full text Add to dashboard Cite

SUMMARY Animals learn to avoid harmful situations by associating a neutral stimulus with a painful one, resulting in a stable threat memory. In mammals, this form of learning requires the amygdala. Although pain is the main driver of aversive learning, the mechanism that transmits pain signals to the amygdala is not well resolved. Here we show that neurons expressing calcitonin gene-related peptide (CGRP) in the parabrachial nucleus are critical for relaying pain signals to the central nucleus of amygdala, and that this pathway may transduce the affective motivational aspects of pain. Genetic silencing of CGRP neurons blocks pain responses and memory formation, while their optogenetic stimulation produces defensive responses and a threat memory. The pain-recipient neurons in the central amygdala expressing CGRP receptors are also critical for establishing a threat memory. The identification of the neural circuit conveying affective pain signals may be pertinent for treating pain conditions with psychiatric comorbidities.

show abstract

Section: Resultsmentioning

confidence: 75%

Elucidating an Affective Pain Circuit that Creates a Threat Memory

Han

Soleiman

Soden

et al. 2015

Cell

358

450

View full text Add to dashboard Cite

show abstract

“…This arrangement is observed in AgRP ‘hunger’ neurons 22 and in that case separate projections to distinct brain regions contribute to various aspects of hunger-related behaviors and physiology 31–33 . CGRP PBN neurons project to the CeA and BNST 3,7 , nuclei that mediate behavioral and physiological responses to ingestive and fear-related stimuli 7,8,34 . Downstream CeA neurons express the CGRP receptor 7 , and a subpopulation of those neurons co-express protein kinase C-δ 7,35 , but the identity of downstream BNST neurons is unknown.…”

Section: Discussionmentioning

confidence: 99%

Encoding of danger by parabrachial CGRP neurons

Campos

Bowen

Roman

et al. 2018

Nature

242

275

View full text Add to dashboard Cite

Animals must respond to various threats to survive. Neurons that express calcitonin gene-related peptide (CGRP) in the parabrachial nucleus (PBN) relay sensory signals that contribute to satiation and pain-induced fear behavior, but it is unknown how they encode these distinct processes. By recording calcium transients in vivo from individual CGRPPBN neurons, we reveal that most neurons are activated by noxious cutaneous (shock, heat, itch) and visceral stimuli (lipopolysaccharide). These same neurons are inhibited during feeding, but become activated during satiation, consistent with evidence that CGRPPBN neurons prevent overeating. CGRPPBN neurons are also activated during consumption of novel food or by an auditory cue that was previously paired with electrical foot shocks. Correspondingly, silencing CGRPPBN neurons attenuates expression of food neophobia and conditioned fear responses. Therefore, in addition to transducing primary sensory danger signals, CGRPPBN neurons promote affective-behavioral states that limit harm in response to potential threats.

show abstract

“…Several putative mechanisms through which the CeA might increase incentive salience have been suggested, involving direct and indirect modulation of mesocorticolimbic (33,34) and brainstem circuits (25,35). Interestingly, in addition to driving sodium and sucrose wanting, the CeA also plays a role in inhibiting feeding in response to satiety cues, conditioned taste aversion, and other anorexigenic signals (36); however, whether these roles involve inhibiting MOR signaling or downstream effects in this region remains to be determined. Intrinsic enkephalin neurons are the major source of endogenous ligand for MORs within the CeA (37,38).…”

Section: Discussionmentioning

confidence: 99%

Endogenous central amygdala mu-opioid receptor signaling promotes sodium appetite in mice

Smith

Walker

Leeboonngam

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Due to the importance of dietary sodium and its paucity within many inland environments, terrestrial animals have evolved an instinctive sodium appetite that is commensurate with sodium deficiency. Despite a well-established role for central opioid signaling in sodium appetite, the endogenous influence of specific opioid receptor subtypes within distinct brain regions remains to be elucidated. Using selective pharmacological antagonists of opioid receptor subtypes, we reveal that endogenous mu-opioid receptor (MOR) signaling strongly drives sodium appetite in sodium-depleted mice, whereas a role for kappa (KOR) and delta (DOR) opioid receptor signaling was not detected, at least in sodium-depleted mice. Fos immunohistochemistry revealed discrete regions of the mouse brain displaying an increased number of activated neurons during sodium gratification: the rostral portion of the nucleus of the solitary tract (rNTS), the lateral parabrachial nucleus (LPB), and the central amygdala (CeA). The CeA was subsequently targeted with bilateral infusions of the MOR antagonist naloxonazine, which significantly reduced sodium appetite in mice. The CeA is therefore identified as a key node in the circuit that contributes to sodium appetite. Moreover, endogenous opioids, acting via MOR, within the CeA promote this form of appetitive behavior.

show abstract

Central amygdala PKC-δ+ neurons mediate the influence of multiple anorexigenic signals

Cited by 321 publications

References 49 publications

Elucidating an Affective Pain Circuit that Creates a Threat Memory

Elucidating an Affective Pain Circuit that Creates a Threat Memory

Encoding of danger by parabrachial CGRP neurons

Endogenous central amygdala mu-opioid receptor signaling promotes sodium appetite in mice

Contact Info

Product

Resources

About