A basal ganglia-like cortical–amygdalar–hypothalamic network mediates feeding behavior

Abstract

<jats:p>The insular cortex (INS) is extensively connected to the central nucleus of the amygdala (CEA), and both regions send convergent projections into the caudal lateral hypothalamus (LHA) encompassing the parasubthalamic nucleus (PSTN). However, the organization of the network between these structures has not been clearly delineated in the literature, although there has been an upsurge in functional studies related to these structures, especially with regard to the cognitive and psychopathological control of feeding. We conducted tract-tracing experiments from the INS and observed a pathway to the PSTN region that runs parallel to the canonical hyperdirect pathway from the isocortex to the subthalamic nucleus (STN) adjacent to the PSTN. In addition, an indirect pathway with a relay in the central amygdala was also observed that is similar in its structure to the classic indirect pathway of the basal ganglia that also targets the STN. C-Fos experiments showed that the PSTN complex reacts to neophobia and sickness induced by lipopolysaccharide or cisplatin. Chemogenetic (designer receptors exclusively activated by designer drugs [DREADD]) inhibition of tachykininergic neurons (Tac1) in the PSTN revealed that this nucleus gates a stop “no-eat” signal to refrain from feeding when the animal is subjected to sickness or exposed to a previously unknown source of food. Therefore, our anatomical findings in rats and mice indicate that the INS-PSTN network is organized in a similar manner as the hyperdirect and indirect basal ganglia circuitry. Functionally, the PSTN is involved in gating feeding behavior, which is conceptually homologous to the motor no-go response of the adjacent STN.</jats:p>

Chronic Distress in Male Mice Impairs Motivation Compromising Both Effort and Reward Processing With Altered Anterior Insular Cortex and Basolateral Amygdala Neural Activation

“…Otherwise, no differences between conditions were found in the other brain regions here studied ( Z < 1.6, all ps > 0.20). Nevertheless, the vast SEM values obtained for the CeA of the CORT condition suggest that this dataset should be replicated or focused on anatomical subdivisions ( Barbier et al, 2020 ) in order to circumvent inaccurate interpretation. Therefore, these results suggest that the GC pharmacological treatment might have impacted effort and reward valuation and processing during PR testing by inducing aberrant functional neural activation and plasticity on aIC and BLA, respectively.…”

Whole-brain activation signatures of weight-lowering drugs

“…The PSTN, PS and SUM were activated by all drugs tested. The PSTN is rapidly activated by ingestion of palatable foods and has been proposed to suppress hedonic feeding behaviour via connections to the CEA and the insular cortex (AI) [ 34 ]. Also, the PS is an integral part of a satiety network involving the PB, CEA and AI [ 32 ].…”

Chronic distress in male mice impairs motivation compromising both effort and reward processing with altered anterior insular cortex and basolateral amygdala neural activation

“…The levels of chronic neural activation addressed by FosB expression after the PR testing are presented in Otherwise, no differences between conditions were found in the other brain regions here studied [Z<1.6, all ps>0.20]. Nevertheless, the vast SEM values obtained for the CeA of the CORT condition suggest that this dataset should be replicated or focus on anatomical subdivisions (Barbier et al, 2020) in order to circumvent inaccurate interpretation. Therefore, these results indicate an impact of the GC pharmacological treatment on effort and reward valuation and processing during PR testing, by inducing aberrant functional neural activation and plasticity on aIC and BLA respectively.…”

“…Indeed, the IC participates in decision-making under uncertainty (Clark, 2010), and the aIC in particular, is involved in contingency acquisition on rodent gambling tasks by modulating reward preference over punishment (Pushparaj et al, 2015). The IC is also relevant for its contribution in initiating feeding behaviour as a part of a basal ganglia-like network (Barbier et al, 2020), and depending on cognitive and emotional influences. Hence, chronic GC exposure could impact animals' motivational state by interfering with aIC-related neural network activity, and disrupt cue-processing associated with food delivery in the PR paradigm.…”