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

Abstract:

: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.

journal_name

Addict Biol

journal_title

Addiction biology

authors

Girven KS,Aroni S,Navarrete J,Marino RAM,McKeon PN,Cheer JF,Sparta DR

doi

10.1111/adb.12961

subject

Has Abstract

pub_date

2020-08-20 00:00:00

pages

e12961

eissn

1355-6215

issn

1369-1600

pub_type

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