6533b859fe1ef96bd12b76d0

RESEARCH PRODUCT

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

subject

description

International audience; The network connecting the insular cortex, the central nucleus of the amygdala, and a caudal hypothalamic nuclear complex including the parasubthalamic nucleus (PSTN) is of interest due to its role in controlling feeding behavior. Here, we show that the organization of this network is similar to that of the basal ganglia network, implying that both fit within a simplified structural plan of the forebrain. Then, we demonstrate that the PSTN complex modulates behavior in response to hedonic factors normally inducing a “reward effect.” The PSTN complex is involved in a “non-feed” response equivalent of a “non-reward” evaluation: “I don’t want to consume this food, recognized as good, because I am not in a conducive emotional or physiological state.”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.