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Top-down circuitry from the anterior insular cortex to VTA dopamine neurons modulates reward-related memory
The insular cortex (IC) has been linked to the processing of interoceptive and exteroceptive signals associated with addictive behavior. However, whether the IC modulates the acquisition of drug-related affective states by direct top-down connectivity with ventral tegmental area (VTA) dopamine neuro...
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Published in: | Cell reports (Cambridge) 2023-11, Vol.42 (11), p.113365-113365, Article 113365 |
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Main Authors: | , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites |
Online Access: | Get full text |
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Summary: | The insular cortex (IC) has been linked to the processing of interoceptive and exteroceptive signals associated with addictive behavior. However, whether the IC modulates the acquisition of drug-related affective states by direct top-down connectivity with ventral tegmental area (VTA) dopamine neurons is unknown. We found that photostimulation of VTA terminals of the anterior insular cortex (aIC) induces rewarding contextual memory, modulates VTA activity, and triggers dopamine release within the VTA. Employing neuronal recordings and neurochemical and transsynaptic tagging techniques, we disclose the functional top-down organization tagging the aIC pre-synaptic neuronal bodies and identifying VTA recipient neurons. Furthermore, systemic administration of amphetamine altered the VTA excitability of neurons modulated by the aIC projection, where photoactivation enhances, whereas photoinhibition impairs, a contextual rewarding behavior. Our study reveals a key circuit involved in developing and retaining drug reward-related contextual memory, providing insight into the neurobiological basis of addictive behavior and helping develop therapeutic addiction strategies.
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•The dopaminergic activity of the VTA is modulated by aIC glutamatergic neurons•The aIC → VTA circuit activity is necessary to express a drug-related contextual reward memory•The photostimulation of the aIC → VTA circuit modulates contextual reward memory•Transsynaptic anterograde tagging from aIC to VTA neurons shows top-down organization
How does the insular cortex modulate reward-related affective states? Hernández-Ortiz et al. disclosed a mechanism by which the aIC modulates drug-related contextual reward memory expression. In particular, the aIC → VTA circuit elicits glutamate releases, which leads to dopamine increases within VTA, related to reward memory expression. |
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ISSN: | 2211-1247 2211-1247 |
DOI: | 10.1016/j.celrep.2023.113365 |