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Abstract
The stomach can be divided into two regions, a proximal (fundus) and a distal (antrum) region. These regions differ in contractile activity. The question is whether the CNS provides region-specific control over the these distinct regions of the stomach. Published findings indicate that the brain has this capacity through afferent inputs to the dorsal motor nucleus of the vagus (DMV), and inhibitory microcircuitry controlling cholinergic outflow to the stomach is comprised of noradrenergic and GABAergic second order neurons. The purpose of my research was to determine the phenotypes of neuron responsible for the inhibitory drive to the DMV which mediates relaxation of the stomach. I used dual-labeling electron microscopy to examine terminals forming synapses with vagal preganglionic neurons which project to the fundus or antrum. I also microinjected norepinephrine into the DMV while recording gastric activity. Analysis of ultrathin sections revealed DBH-IR and PNMT-IR terminals and dendrites, and GAD67-IR terminals. Fundus and antrum-projecting profiles were found throughout the DMV, especially at levels paralleling the area postrema. Examination of 482 synapses on 238 DMV fundus-projecting profiles revealed that 17.4 +/- 2.7%, (n=4), synaptic contacts were with DBH-IR terminals. Of 165 fundus-projecting profiles, 4.4 +/- 1.5%, (n=4), formed synaptic contacts with PNMT-IR terminals. These data indicate that the main catecholaminergic input to DMV fundus neurons is noradrenergic. Examination of 384 synapses on 223 antrum-projecting profiles revealed no synaptic contact with DBH-IR terminals. Examination of 214 synapses on 195 DMV antrum-projecting profiles revealed that 23.0 +/- 3.6%, (n=4), of synaptic contacts were with GAD67-IR terminals. The examination of 220 synapses on 203 fundus-projecting profiles, revealed 7.9 +/-3.1%, (n=4), formed synaptic contacts with GAD67-IR terminals. These data fit the hypothesis that within the DMV, norepinephrine is a key neurotransmitter that controls neurons innervating the fundus, whereas GABA is a key neurotransmitter that controls neurons which innervate the antrum. Consistent with norepinephrine acting as a synaptic neurotransmitter at DMV fundus-projecting neurons were findings that microinjection of norepinephrine (100 pmol) into the DMV decreased fundus tone using the strain gauge technique. These data suggest that the CNS can provide region-specific control over gastric function.
