Obesity has significant consequences in terms of medical cost and quality of life. Eating and body weight are both genetically influenced while also clearly sensitive to the food environment. It is clear that our inability to control intake of readily available food is central to this problem. In essence, this is similar to drug addiction where people want to control a behavior, but struggle to do so. Human imaging data implicates regions of the cortex in this type of self-regulation and decision-making. Studies in animal models of addiction support an important role for prefrontal cortex (PFC) in craving and intake. However, most studies of feeding in animal models have not included the cortex, with prominent models primarily focused on hypothalamic circuits. This proposal aims to fill in this gap by incorporating the PFC into our views and models of intake control. Preliminary data establish that optogenetic stimulation of dopamine receptor type 1 (D1) pyramidal neurons of the PFC is sufficient to increase food intake. Additional circuit analysis identifies the basolateral amygdala (BLA) as a potential target region mediating these effects. The proposed work will interrogate this novel D1 PFC to amygdala circuit while also connecting it with other brain regions that are known to influence feeding. This work is important, as it will expand our neural models of feeding and begin to bridge the gap between rodent and human studies.

Public Health Relevance

The failure to control food intake contributes to increased rates of obesity, and subsequent negative effects on health and medical costs. Many brain areas influence motivation and decisions to eat, but previous work has not elucidated the role of the cortex. The proposed experiments will explore the molecular and neural basis for how the cortex influences eating behavior.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK098994-02
Application #
8641355
Study Section
Neuroendocrinology, Neuroimmunology, Rhythms and Sleep Study Section (NNRS)
Program Officer
Hyde, James F
Project Start
2013-04-01
Project End
2018-02-28
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
2
Fiscal Year
2014
Total Cost
$308,633
Indirect Cost
$91,133
Name
Yale University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Land, Benjamin B; Narayanan, Nandakumar S; Liu, Rong-Jian et al. (2014) Medial prefrontal D1 dopamine neurons control food intake. Nat Neurosci 17:248-53