Regulation of gastrointestinal function by the brain is an important but inadequately understood component of energy homeostasis in humans. The long-term objective of this project is to understand the local neuronal connectivity in the brainstem solitary complex. As the site of first central synaptic contact for sensory afferent fibers of the vagus nerve from the digestive tract, neurons in the nucleus tractus solitarius (NTS) process digestive system information prior to further integration via higher brain areas and eventual activation of motor output to the stomach. Included in the neuronal circuits controlling autonomic function are local synaptic circuits in the NTS, inputs from CNS regions outside the solitary complex, and reflex-circuit interactions with vagal motor neurons in the dorsal motor nucleus of the vagus nerve (DMV). Although the neuronal circuitry of the caudal solitary complex is the functional substrate for visceral sensory-motor integration relating to feeding behavior, local synaptic connectivity in the area has not been adequately described. We will use whole-cell patch-clamp recordings in brain slices to investigate the functional organization of the caudal solitary complex. We will identify neurons on the basis of their functional connections with the proximal stomach using in vivo labeling methods. We will also correlate synaptic responses with quantitative morphological features using biocytin labeling techniques. Both electrical stimulation of primary viscerosensory input and photoactivation of caged glutamate to stimulate discrete sites within the slice will be used to investigate the local amino acid-mediated synaptic circuitry of the region.
The specific aims of the proposal are designed to test hypotheses regarding the synaptic circuitry of the solitary complex. The specific hypotheses for the proposed research are: 1) Gastric-related principal neurons in the NTS are inhibited by a convergent system of local GABAergic neurons (i.e., lateral inhibition); 2) small, putative inhibitory NTS neurons are activated by local excitatory NTS neurons; and 3) stomach-projecting neurons in the DMV are directly inhibited by NTS input. These experiments will result in an understanding of neuronal connectivity within the NTS and between regions of the solitary complex. This information is highly relevant to the mechanistic understanding of feeding behaviors such as receptive relaxation and accommodation in the stomach. It will also enhance understanding of the mechanisms of action for treatments of digestive system-related disorders.
Showing the most recent 10 out of 32 publications
