Electrophysiological and morphological properties of pre-autonomic neurones in the rat hypothalamic paraventricular nucleus.

The paraventricular nucleus (PVN) of the hypothalamus is an important integrating site for autonomic and endocrine function (Swanson & Sawchenko, 1980). This nucleus is a complex heterogeneous region consisting of magnocellular and parvocellular neurones that are largely segregated into specific anatomical compartments (Swanson & Sawchenko, 1983). The parvocellular PVN comprises different neuronal types, including neuroendocrine neurones that project to the median eminence and regulate the release of hormones from the anterior pituitary gland, and pre-autonomic neurones that send long descending projections to brainstem and spinal cord regions that are important with respect to autonomic control. These include areas in the ventral and dorsal medulla, such as the nucleus of the tractus solitarius (NTS), the dorsal motor nucleus of the vagus (DMX) and the rostral ventrolateral medulla (RVLM) (Armstrong et al. 1980; Swanson & Kuypers, 1980). Both anatomical and electrophysiological studies also demonstrate that sympathetic preganglionic motoneurones located in the intermediolateral cell column of the thoraco-lumbar spinal cord are directly innervated by neurones in the PVN (Saper et al. 1976; Coote et al. 1998; Ranson et al. 1998), whose firing activity was shown to follow changes in blood pressure (Lovick & Coote, 1988). A large bulk of physiological data supports a role for the PVN in cardiovascular function. For example, the PVN has been shown to play a role in the control of the baroreceptor reflex (Zhang & Ciriello, 1985a) Zhang & Ciriello, 1985b Electrical and chemical activation of the PVN evoked vasodilatation and vasoconstrictor responses, with concomitant changes in blood pressure (Porter & Brody 1985, Porter 1985,1986; Kannan et al. 1988; Malpas & Coote, 1994). Parvocellular neurones located in the medial and ventral subdivisions of the PVN are activated during haemorrhage (Badoer et al. 1993), and changes in renal sympathetic nerve discharge have also been attributed to PVN activation (Kannan et al. 1988). Moreover, it has been suggested that the PVN is involved in the development and/or maintenance of cardiovascular-related diseases such as hypertension (Goto et al. 1981; Ciriello et al. 1984) and ischaemic heart failure (Patel & Zhang, 1996; Patel et al. 2000). Despite the strong evidence for the PVN as an important site for cardiovascular control, less is known about the cytoarchitectural and physiological properties of identified PVN pre-autonomic parvocellular neurones. Recently, Barrett-Jolley et al. (2000) demonstrated the expression of voltage-gated K+ (Kv) currents in dissociated PVN neurones, retrogradely identified as projecting to the intermediolateral column in the spinal cord. Although previous in vitro studies have looked in detail into the electrophysiological properties of PVN neurones, none of these studies were carried out on identified PVN neurones projecting to autonomic-related areas (Hoffman et al. 1991; Tasker & Dudek, 1991; Luther & Tasker, 2000). In the present study, identification of PVN pre-autonomic neurones was achieved by combining in vivo anatomical retrograde tracing techniques with in vitro patch-clamp recordings of labelled neurones visualized in adult hypothalamic brain slices. Using these techniques, a detailed characterization of the cellular properties of identified PVN pre-autonomic neurones was obtained. These results indicate that even though PVN pre-autonomic neurones display distinctive morphological and electrical properties that distinguish them from other PVN neuronal types, they constitute a heterogeneous neuronal population.