Zona incerta neurons projecting to the ventral tegmental area promote action initiation towards feeding

Key pointsThe zona incerta (ZI) and ventral tegmental area (VTA) are brain areas that are both implicated in feeding behaviour. The ZI projects to the VTA, although it has not yet been investigated whether this projection regulates feeding.We experimentally (in)activated the ZI to VTA projection by using dual viral vector technology, and studied the effects on feeding microstructure, the willingness to work for food, general activity and body temperature.Activity of the ZI to VTA projection promotes feeding by facilitating action initiation towards food, as reflected in meal frequency and the willingness to work for food reward, without affecting general activity or directly modulating body temperature.We show for the first time that activity of the ZI to VTA projection promotes feeding, which improves the understanding of the neurobiology of feeding behaviour and body weight regulation.Both the zona incerta (ZI) and the ventral tegmental area (VTA) have been implicated in feeding behaviour. The ZI provides prominent input to the VTA, although it has not yet been investigated whether this projection regulates feeding. Therefore, we investigated the role of ZI to VTA projection neurons in the regulation of several aspects of feeding behaviour. We determined the effects of (in)activation of ZI to VTA projection neurons on feeding microstructure, food-motivated behaviour under a progressive ratio schedule of reinforcement, locomotor activity and core body temperature. To activate or inactivate ZI neurons projecting to the VTA, we used a combination of canine adenovirus-2 in the VTA, as well as Cre-dependent designer receptors exclusively activated by designer drugs (DREADD) or tetanus toxin (TetTox) light chain in the ZI. TetTox-mediated inactivation of ZI to VTA projection neurons reduced food-motivated behaviour and feeding by reducing meal frequency. Conversely, DREADD-mediated chemogenetic activation of ZI to VTA projection neurons promoted food-motivated behaviour and feeding. (In)activation of ZI to VTA projection neurons did not affect locomotor activity or directly regulate core body temperature. Taken together, ZI neurons projecting to the VTA exert bidirectional control overfeeding behaviour. More specifically, activity of ZI to VTA projection neurons facilitate action initiation towards feeding, as reflected in both food-motivated behaviour and meal initiation, without affecting general activity

Structure-activity relationships of pentamidine-affected ion channel trafficking and dofetilide mediated rescue

Medicinal Chemistr

Individual differences in voluntary alcohol intake in rats: relationship with impulsivity, decision making and Pavlovian conditioned approach

RATIONALE: Alcohol use disorder (AUD) has been associated with suboptimal decision making, exaggerated impulsivity, and aberrant responses to reward-paired cues, but the relationship between AUD and these behaviors is incompletely understood. OBJECTIVES: This study aims to assess decision making, impulsivity, and Pavlovian-conditioned approach in rats that voluntarily consume low (LD) or high (HD) amounts of alcohol. METHODS: LD and HD were tested in the rat gambling task (rGT) or the delayed reward task (DRT). Next, the effect of alcohol (0-1.0 g/kg) was tested in these tasks. Pavlovian-conditioned approach (PCA) was assessed both prior to and after intermittent alcohol access (IAA). Principal component analyses were performed to identify relationships between the most important behavioral parameters. RESULTS: HD showed more optimal decision making in the rGT. In the DRT, HD transiently showed reduced impulsive choice. In both LD and HD, alcohol treatment increased optimal decision making in the rGT and increased impulsive choice in the DRT. PCA prior to and after IAA was comparable for LD and HD. When PCA was tested after IAA only, HD showed a more sign-tracking behavior. The principal component analyses indicated dimensional relationships between alcohol intake, impulsivity, and sign-tracking behavior in the PCA task after IAA. CONCLUSIONS: HD showed a more efficient performance in the rGT and DRT. Moreover, alcohol consumption enhanced approach behavior to reward-predictive cues, but sign-tracking did not predict the level of alcohol consumption. Taken together, these findings suggest that high levels of voluntary alcohol intake are associated with enhanced cue- and reward-driven behavior