Cellular heterogeneity within the solitary tract nucleus and visceral afferent processing - Electrophysiological approaches to discerning pathway performance

Many homeostatic reflexes depend on autonomic central nervous system mechanisms to systemically coordinate visceral organ function. The nucleus of the solitary tract (NTS) is the common entry of cranial visceral afferents into these regulatory pathways. Such NTS neurons initiate adjustments in cardiovascular, respiratory, gastrointestinal and other visceral systems. Diversity of neurons within the NTS appears integral to such processing but is daunting to approach experimentally. This review outlines three experimental approaches to understanding cellular heterogeneity within NTS and its relation to function. Brainstem slice preparations coupled with patch recordings afford cellular-molecular resolution with substantial links to the more intact system. Pharmacological approaches based on visceral afferent phenotype have helped identify myelinated and unmyelinated solitary tract inputs to NTS neurons. An interesting outcome has been the robust association of A-type potassium currents with NTS neurons receiving unmyelinated afferents. Neuroanatomical tracers offer a second, complementary approach. Anterograde transport of fluorescent dye identifies cranial visceral afferent terminals on second order neurons that cluster on or proximal to the soma - a highly unusual distribution in the central nervous system. Thus, second order baroreceptive neurons can be identified neuroanatomically in vitro. Equally helpful has been identification of NTS projection neurons by retrograde tracers injected into target regions of the hypothalamus or brainstem and this approach indicates substantial specialization - relative homogeneous neurons within the overall heterogeneity of NTS. Lastly, transgenic mouse strains, particularly those expressing marker chromophores, have identified phenotypic subtypes such as GABAergic inhibitory neurons within NTS. Combined methodologies are forging new understanding of NTS and autonomic regulation.