Kavli Affiliate: Zachary Knight & Jeffrey M. Friedman
| Authors: Christin Kosse, Jessica Ivanov, Zachary Knight, Kyle Pellegrino and Jeffrey Friedman
| Summary:
The brain processes an array of stimuli enabling the selection of an appropriate behavioural response but the underlying circuitry linking inputs to outputs is unknown. Here we delineate a subcortical circuit in which brain-derived neurotrophic factor (BDNF) expressing neurons in the ventromedial hypothalamus (VMH) directly connect interoceptive inputs to motor centers controlling food consumption. VMHBDNF neuron inhibition increases food intake by gating motor sequences of feeding through projections to premotor areas in the brainstem. When food is unavailable, VMHBDNF inhibition elicits consummatory behaviors directed at inanimate objects such as a wooden block. The activity of these neurons decreases prior to food consumption and increases when food is in proximity but not consumed. Their activity is higher in diet-induced obese animals dand also increased by leptin. VMHBDNF neurons receive monosynaptic inputs from both agouti-related peptide (AgRP) and proopiomelanocortin (POMC) neurons in the arcuate nucleus (Arc) and AgRP inputs to these neurons increase food consumption. In addition, the orexigenic effect of AgRP neuron activation is blocked when VMHBDNF neurons are also activated. These data identify a ArcAgRP→VMHBDNF→brainstem circuit that senses the energy state of an animal and elicits consummatory behaviors to control body weight.