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

Obesity affects brain structure and function- rescue by bariatric surgery?

Contains fulltext : 219675.pdf (Publisher’s version ) (Open Access)Obesity has a major impact on metabolic health thereby negatively affecting brain function and structure, however mechanisms involved are not entirely understood. The increasing prevalence of obesity is accompanied by a growing number of bariatric surgeries (BS). Weight loss after BS appears to improve cognitive function in patients. Therefore, unraveling mechanisms how BS influences brain function may be helpful to develop novel treatments or treatments in combination with BS preventing/inhibiting neurodegenerative disorders like Alzheimer's disease. This review shows the relation between obesity and impaired circulation to and in the brain, brain atrophy, and decreased cognitive functioning. Weight loss seems to recover some of these brain abnormalities as greater white matter and gray matter integrity, functional brain changes and increased cognitive functioning is seen after BS. This relation of body weight and the brain is partly mediated by changes in adipokines, gut hormones and gut microbiota. However, the exact underlying mechanisms remain unknown and further research should be performed