Glutamatergic input from the insula to the ventral bed nucleus of the stria terminalis controls reward-related behavior.

Autor: Girven KS; Program in Neuroscience, University of Maryland Baltimore, Baltimore, Maryland, USA.; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA., Aroni S; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA., Navarrete J; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA., Marino RAM; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA., McKeon PN; Program in Molecular Medicine, University of Maryland Baltimore, Baltimore, Maryland, USA., Cheer JF; Program in Neuroscience, University of Maryland Baltimore, Baltimore, Maryland, USA.; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.; Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, USA., Sparta DR; Program in Neuroscience, University of Maryland Baltimore, Baltimore, Maryland, USA.; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
Jazyk: angličtina
Zdroj: Addiction biology [Addict Biol] 2021 May; Vol. 26 (3), pp. e12961. Date of Electronic Publication: 2020 Aug 20.
DOI: 10.1111/adb.12961
Abstrakt: Individuals suffering from substance use disorder often experience relapse events that are attributed to drug craving. Insular cortex (IC) function is implicated in processing drug-predictive cues and is thought to be a critical substrate for drug craving, but the downstream neural circuit effectors of the IC that mediate reward processing are poorly described. Here, we uncover the functional connectivity of an IC projection to the ventral bed nucleus of the stria terminalis (vBNST), a portion of the extended amygdala that has been previously shown to modulate dopaminergic activity within the ventral tegmental area (VTA), and investigate the role of this pathway in reward-related behaviors. We utilized ex vivo slice electrophysiology and in vivo optogenetics to examine the functional connectivity of the IC-vBNST projection and bidirectionally control IC-vBNST terminals in various reward-related behavioral paradigms. We hypothesized that the IC recruits mesolimbic dopamine signaling by activating VTA-projecting, vBNST neurons. Using slice electrophysiology, we found that the IC sends a glutamatergic projection onto vBNST-VTA neurons. Photoactivation of IC-vBNST terminals was sufficient to reinforce behavior in a dopamine-dependent manner. Moreover, silencing the IC-vBNST projection was aversive and resulted in anxiety-like behavior without affecting food consumption. This work provides a potential mechanism by which the IC processes exteroceptive triggers that are predictive of reward.
(© 2020 Society for the Study of Addiction.)
Databáze: MEDLINE