A Central Amygdala CRF Circuit Facilitates Learning about Weak Threats

Sanford, Christina A.; Soden, Marta E.; Baird, Madison A.; Miller, Shannon M.; Schulkin, Jay; Palmiter, Richard D.; Clark, Michael; Zweifel, Larry S.

doi:10.1016/j.neuron.2016.11.034

Cited by 156 publications

(187 citation statements)

References 60 publications

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“…Cell-type specific studies have shown evidence for the involvement of several genetically defined CeA neurons in aversive behaviors such as defensive responses and anxiogenesis (Andero et al, 2014; Han et al, 2015; Haubensak et al, 2010; Isosaka et al, 2015; Li et al, 2013; McCall et al, 2015; Pomrenze et al, 2015; Sanford et al, 2017). However, despite early evidence suggesting the involvement of the CeA in appetitive behaviors (Galaverna et al, 1993; Gallagher et al, 1990; Parkinson et al, 2000; Ritter and Hutton, 1995) and more recent activation studies demonstrating a modulatory role of the CeA in appetitive behaviors (Cai et al, 2014; Robinson et al, 2014; Seo et al, 2016), how appetitive behavior integrates into a structural and functional model of amygdala has yet to be established.…”

Section: Introductionmentioning

confidence: 99%

Basolateral to Central Amygdala Neural Circuits for Appetitive Behaviors

Kim

Zhang

Muralidhar

et al. 2017

Neuron

353

485

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Summary Basolateral amygdala (BLA) principle cells are capable of driving and antagonizing behaviors of opposing valence. BLA neurons project to the central amygdala (CeA), which also participates in negative and positive behaviors. However, the CeA has primarily been studied as the site for negative behaviors and the causal role for CeA circuits underlying appetitive behaviors is poorly understood. Here we identified several genetically distinct populations of CeA neurons that mediate appetitive behaviors and dissected the BLA to CeA circuit for appetitive behaviors. Protein phosphatase 1 regulatory subunit 1B+ BLA pyramidal neurons to dopamine receptor 1+ CeA neurons define a pathway for promoting appetitive behaviors, while R-spondin 2+ BLA pyramidal neurons to dopamine receptor 2+ CeA neurons define a pathway for suppressing appetitive behaviors. These data reveal genetically defined neural circuits in the amygdala that promote and suppress appetitive behaviors analogous to the direct and indirect pathway of the basal ganglia.

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Section: Introductionmentioning

confidence: 99%

Basolateral to Central Amygdala Neural Circuits for Appetitive Behaviors

Kim

Zhang

Muralidhar

et al. 2017

Neuron

353

485

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“…Subsequently, CRH‐expressing neurons and receptors have been identified throughout selective regions of the brain, where they orchestrate the peptide's influence on numerous brain functions, typically in response to stress or threat (Joëls & Baram, ). For example, amygdalar CRH has been implicated in fear and anxiety (Pomrenze et al, ; Regev et al, ; Regev, Tsoory, Gil, & Chen, ; Sanford et al, ; Wang et al, ); hippocampal CRH contributes to stress‐related memory changes (Chen et al, ; Maras & Baram, ); CRH terminals in the locus ceruleus contribute to stress‐related neurotransmission (Van Bockstaele & Valentino, ); and CRH‐positive fibers in the VTA influence dopamine release (George, Le Moal, & Koob, ).…”

Section: Introductionmentioning

confidence: 99%

New viral‐genetic mapping uncovers an enrichment of corticotropin‐releasing hormone‐expressing neuronal inputs to the nucleus accumbens from stress‐related brain regions

Itoga

Chen

Fateri

et al. 2019

J of Comparative Neurology

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Corticotropin‐releasing hormone (CRH) is an essential, evolutionarily‐conserved stress neuropeptide. In addition to hypothalamus, CRH is expressed in brain regions including amygdala and hippocampus where it plays crucial roles in modulating the function of circuits underlying emotion and cognition. CRH+ fibers are found in nucleus accumbens (NAc), where CRH modulates reward/motivation behaviors. CRH actions in NAc may vary by the individual's stress history, suggesting roles for CRH in neuroplasticity and adaptation of the reward circuitry. However, the origin and extent of CRH+ inputs to NAc are incompletely understood. We employed viral genetic approaches to map both global and CRH+ projection sources to NAc in mice. We injected into NAc variants of a new designer adeno‐associated virus that permits robust retrograde access to NAc‐afferent projection neurons. Cre‐dependent viruses injected into CRH‐Cre mice enabled selective mapping of CRH+ afferents. We employed anterograde AAV1‐directed axonal tracing to verify NAc CRH+ fiber projections and established the identity of genetic reporter‐labeled cells via validated antisera against native CRH. We quantified the relative contribution of CRH+ neurons to total NAc‐directed projections. Combined retrograde and anterograde tracing identified the paraventricular nucleus of the thalamus, bed nucleus of stria terminalis, basolateral amygdala, and medial prefrontal cortex as principal sources of CRH+ projections to NAc. CRH+ NAc afferents were selectively enriched in NAc‐projecting brain regions involved in diverse aspects of the sensing, processing and memory of emotionally salient events. These findings suggest multiple, complex potential roles for the molecularly‐defined, CRH‐dependent circuit in modulation of reward and motivation behaviors.

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“…The amygdala sits at the intersection between learning and motivation and has been shown to ascribe motivational and emotional valence to rewarding and aversive cues and outcomes (Baxter & Murray, ; DiFeliceantonio & Berridge, ; Janak & Tye, ; Mahler & Berridge, ; Sanford et al., ). Beyond its role in fear‐related behaviours, the amygdala has been shown to be involved in drug addiction (Makris et al., ; Wrase et al., ; Xie et al., ; Zill et al., ).…”

Section: Introductionmentioning

confidence: 99%

Optogenetic activation of the central amygdala generates addiction‐like preference for reward

Tom

Ahuja

Maniates

et al. 2018

Eur J of Neuroscience

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Drug and behavioural addictions are characterized by an intense and focused pursuit of a single reward above all others. Pursuit of the addictive reward is often compulsively sought despite adverse consequences and better alternative outcomes. Here, we explored the ability of the central amygdala (CeA) to powerfully bias choice, causing specific rewards to be almost compulsively preferred. Rats were trained on an operant choice task in which they could choose to respond on either of the two levers to receive a sucrose reward, one of which was paired with optogenetic stimulation of the CeA using channelrhodopsin-2 (ChR2). Rats developed an almost exclusive preference for the laser-paired reward over the otherwise equal unpaired reward. We found that this preference for stimulation-paired reward persists even when a much larger sucrose reward is offered as an alternative (contingency management) or when this preferred reward is paired with adverse consequences such as progressively larger electric foot shock, time delays or effort requirements. We also report that when challenged with foot shock, a small proportion of these animals (≈20%) retained an exclusive laser-paired reward preference, whereas others began to seek the alternate reward when the shock reached high levels. Lastly, we confirmed that optogenetic CeA stimulation was not independently rewarding if delivered in the absence of a paired sucrose reward. These results suggest a role for the CeA in focusing motivation and desire to excessive levels, generating addiction-like behaviour that persists in the face of more rewarding alternatives and adverse consequences.

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A Central Amygdala CRF Circuit Facilitates Learning about Weak Threats

Cited by 156 publications

References 60 publications

Basolateral to Central Amygdala Neural Circuits for Appetitive Behaviors

Basolateral to Central Amygdala Neural Circuits for Appetitive Behaviors

New viral‐genetic mapping uncovers an enrichment of corticotropin‐releasing hormone‐expressing neuronal inputs to the nucleus accumbens from stress‐related brain regions

Optogenetic activation of the central amygdala generates addiction‐like preference for reward

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