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Glutamatergic input from the insula to the ventral bed nucleus of the stria terminalis controls reward‐related behavior
Author(s) -
Girven Kasey S.,
Aroni Sonia,
Navarrete Jovana,
Marino Rosa A.M.,
McKeon Paige N.,
Cheer Joseph F.,
Sparta Dennis R.
Publication year - 2021
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12961
Subject(s) - stria terminalis , ventral tegmental area , neuroscience , glutamatergic , ventral pallidum , optogenetics , dopamine , nucleus accumbens , amygdala , psychology , dopaminergic , central nucleus of the amygdala , reward system , biology , basal ganglia , glutamate receptor , globus pallidus , central nervous system , receptor , biochemistry
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.