Glutamatergic basolateral amygdala to anterior insular cortex circuitry maintains rewarding contextual memory

Abstract

Findings have shown that anterior insular cortex (aIC) lesions disrupt the maintenance of drug addiction, while imaging studies suggest that connections between amygdala and aIC participate in drug-seeking. However, the role of the BLA → aIC pathway in rewarding contextual memory has not been assessed. Using a cre-recombinase under the tyrosine hydroxylase (TH+) promoter mouse model to induce a real-time conditioned place preference (rtCPP), we show that photoactivation of TH+ neurons induced electrophysiological responses in VTA neurons, dopamine release and neuronal modulation in the aIC. Conversely, memory retrieval induced a strong release of glutamate, dopamine, and norepinephrine in the aIC. Only intra-aIC blockade of the glutamatergic N-methyl-D-aspartate receptor accelerated rtCPP extinction. Finally, photoinhibition of glutamatergic BLA → aIC pathway produced disinhibition of local circuits in the aIC, accelerating rtCPP extinction and impairing reinstatement. Thus, activity of the glutamatergic projection from the BLA to the aIC is critical for maintenance of rewarding contextual memory.

Prior Cocaine Exposure Increases Firing to Immediate Reward While Attenuating Cue and Context Signals Related to Reward Value in the Insula

“…Further, it has been shown that damage to insula can promote drug abstinence (Naqvi et al, 2007). Rodent work has supported these ideas by showing that disruption of insula function reduces the ability of drug-associated cues and contexts to drive drug-seeking (Contreras et al, 2007;Forget et al, 2010;Perdomo et al, 2012;Seif et al, 2013;García et al, 2013;Li et al, 2013;Pelloux et al, 2013;Pushparaj and Le Foll, 2015;Cofresí et al, 2018;Campbell et al, 2019;Zhang et al, 2019;Gil-Lievana et al, 2020).…”

Calcium-Permeable AMPA Receptor Activity and GluA1 Trafficking in the Basolateral Amygdala Regulate the Positive Reinforcing Effects of Alcohol

“…Although these data demonstrate alcohol-induced changes in CP-AMPAR signaling in BLA-NAcb projection neurons, they do not address the generality of alcohol’s effects across multiple circuits. Topographically overlapping neurons in the BLA send glutamatergic projections to multiple regions that regulate aspects of reward and aversion, such as the insular cortex and central amygdala (CeA) 70,71 , that may differentially alter alcohol self-administration 72 . Future studies utilizing retrobead strategies can evaluate alterations in CP-AMPAR signaling in these and in other BLA projection regions.…”

Optoception: perception of optogenetic brain stimulation

“…In another behavioral task, we tested whether mice could categorize laser frequencies. That is, the lower frequencies (10, 12, and 14 Hz) were rewarded if mice went to the left port, and higher frequencies (16,18, and 20 Hz) were rewarded if they went to the right port (Fig. 3E; ports were counterbalanced).…”