Electrophysiological and morphological heterogeneity of rat dorsal vagal neurones which project to specific areas of the gastrointestinal tract

The electrophysiological properties of rat dorsal motor nucleus of the vagus (DMV) neurones (n = 162) were examined using whole cell patch clamp recordings from brainstem slices. Recordings were made from DMV neurones whose projections to the gastrointestinal tract had been identified by previously applying fluorescent retrograde tracers to the gastric fundus, corpus or antrum/pylorus, or to the duodenum or caecum. The neuronal groups were markedly heterogeneous with respect to several electrophysiological properties. For example, neurones which projected to the fundus had a higher input resistance (400 ± 25 MΩ), a smaller and shorter after-hyperpolarization (16.7 ± 0.49 mV and 63.5 ± 3.9 ms) and a higher frequency of action potential firing (19.3 ± 1.4 action potentials s−1) following injection of depolarizing current (270 pA) when compared with caecum-projecting neurones (302 ± 22 MΩ; 23.5 ± 0.87 mV and 81.1 ± 5.3 ms; 9.7 ± 1.1 action potentials s−1; P < 0.05 for each parameter). Differences between neuronal groups were also apparent with respect to the distribution of several voltage-dependent potassium currents. Inward rectification was present only in caecum-projecting neurones, for example. Neurones (n = 82) were filled with the intracellular stain Neurobiotin allowing post-fixation morphological reconstruction. Neurones projecting to the caecum had the largest cell volume (5238 ± 535 μm3), soma area (489 ± 46 μm2) and soma diameter (24.6 ± 1.24 μm) as well as the largest number of dendritic branch segments (23 ± 2). In summary, these results suggest that DMV neurones are heterogeneous with respect to some electrophysiological as well as some morphological properties and can be divided into subgroups according to their gastrointestinal projections. The vagus nerve is the source of parasympathetic innervation to the gastrointestinal (GI) tract and plays a major role in the regulation of GI motility as well as gastric acid and pancreatic endocrine/exocrine secretion. The parasympathetic motor innervation to the major portion of the GI tract is provided by neurones in the dorsal motor nucleus of the vagus (DMV) (Gillis et al. 1989). Retrograde tracing experiments have shown the existence of a viscerotopic medio-lateral columnar organization that spans the entire rostro-caudal extent of the rat DMV (Fox & Powley, 1985; Shapiro & Miselis, 1985; Norgren & Smith, 1988). The medial portion of the DMV contains the somata of neurones which project to stomach and proximal intestine, while the more lateral tips of the DMV contain the somata of preganglionic neurones projecting to the distal intestine (Altschuler et al. 1991; Berthoud et al. 1991). Numerous studies have reported diverse morphological features of rat DMV neurones, mainly in their dendritic extent (Rinaman et al. 1989; Rinaman & Miselis, 1990; Fox & Powley, 1992) but also in their somata size or shape (Zhang et al. 1995; Fogel et al. 1996; Jarvinen & Powley, 1999). Fogel et al. (1996) have recently provided strong evidence for the existence of a relationship between structure and function in the DMV. These authors used in vivo techniques to demonstrate that DMV neurones responsive to gastric or intestinal distension can be classified into four separate morphological groups. A feature of these subgroups is that the extracellular recorded action potentials in all the groups have a different shape (Fogel et al. 1996), which would suggest the possibility of an underlying different arrangement of electrical membrane properties within DMV neurones. Such diversity in electrophysiological properties is also supported by previous reports of a large array of unevenly distributed membrane currents in DMV neurones (Travagli et al. 1992; Sah & McLachlan, 1992b, 1993; Travagli & Gillis, 1994, 1995; Dean et al. 1997; Bertolino et al. 1997). Travagli and colleagues, among others, have shown that the distribution of the potassium inward rectifier (IK(IR)), as well as the non-selective cationic current (IH), is not uniform among DMV neurones (Travagli & Gillis, 1994). A recent hypothesis proposed that a sensory-motor lattice underlies the control of vago-vagal reflexes, one of the corollaries being that the location of the DMV neurone determines the nature of their electrophysiological as well as morphological characteristics (Powley et al. 1992). Indeed, neurones containing the non-selective cationic current IH are more likely to be located in the medial portion of the DMV, strongly resembling the distribution of gastric vagal motoneurones (Travagli & Gillis, 1994). Also, the extent and orientation of the DMV neuronal arbor was shown to vary along the rostro-caudal and medio-lateral boundaries of the nucleus (Fox & Powley, 1992). In addition, a recent analysis of DMV neurones correlated their response to stimulation of different regions of the GI tract with their soma-dendritic morphology and concluded that certain features of DMV architecture are indeed associated with specific functions (Fogel et al. 1996). To this end, the electrophysiological and morphological characteristics of DMV neurones have not yet been linked to a particular motoneurone output. The purpose of this study therefore was to correlate the electrical and morphological properties of DMV neurones with their GI projections. Preliminary accounts of these data have been presented previously (Travagli et al. 1998).