Sensory-information from the gastrointestinal tract modifies vagal control of gastrointestinal activity. We know that the nucleus of the solitary tract (NST) is the principle recipient of this sensory input, but we do not as yet know how the NST processes and transmits this essential information. NST neurons vary in size, shape, dendritic architecture, response properties and axonal projections. We believe that this functional and structural heterogeneity indicates different types of NST neurons serving different functions. The proposed studies are based on the following hypotheses: 1) NST neurons responsive to stimulation of duodenal or gastric mechano-, chemo - or osmoreceptors are functionally heterogeneous. Neurons can be classified as unimodal (cells with narrow breadth of tuning, i.e. respond to only one type of input from a single receptive field) or multimodal. This latter group can a) receive convergent information from stomach and duodenum (quality-specific) and/or b) receive more than one quality-specific type of information from the stomach or duodenum. For multimodal neurons, stimuli may have a similar effect on neuronal activity (nonspecific responders) or different effects (discriminators). 2) Morphological features are related to responsivity of NST neurons. Specifically, a) NST neurons that receive either duodenal or gastric stimuli alone have dendrites in the duodenal or gastric region of the NST only. Neurons expressing convergence either have dendrites in both regions or have dendritic arbors in the NST regions that receive primary vagal afferents from both the stomach and duodenum; b) Multimodal NST neurons have a different dendritic architecture than unimodal neurons.
Specific Aim 1 is designed to distinguish NST neurons by changes in neurophysiological activity (firing rate and pattern) in response to stimulation of gastric or duodenal mechano-, chemo- and osmoreceptors.
Specific Aim 2 proposes to determine the NST coordinates, soma size and shape, dendritic architecture and axonal projections of the physiologically-characterized NST neurons. We will use the intracellular injection of Neurobiotin to label individual physiologically-characterized NST neurons that respond to intestinal stimuli. Using computerized three-dimensional reconstruction techniques, we will determine the morphological characteristics which are correlated with specific physiological response properties. At the conclusion of the proposed funding period, we expect to have described the responsivity features that distinguish NST neurons and learn how sensory information is processed in the NST. We will have described the morphological characteristics of the physiologically characterized cells and identified structural features that correlate with function. Finally, we will have determined the destinations for quality-specific information. This information is necessary to understand the mechanisms by which the CNS control of gastrointestinal function is modulated by afferent input.
