Neurotensin in the lateral hypothalamic area: origin and function

Abstract

The origin of neurotensin in the lateral hypothalamus was investigated by means of fluorescent retrograde tract tracing and neurotensin-like immunoreactivity. Following fluorescent retrograde tract tracing with FluoroGold combined with neurotensin immunohistochemistry in the rat brain, numerous neurotensin-immunoreactive neurons with projections to the posterior lateral hypothalamic area were identified in the central nucleus of the amygdala, perifornical area and the parabrachial nucleus. Fewer numbers of neurotensin-positive neurons with projections to the lateral hypothalamic area were observed in the bed nucleus of the stria terminalis, lateral septal nucleus, medial preoptic area, peri- and paraventricular nuclei of the hypothalamus, anterior lateral hypothalamic area and dorsal raphe nucleus. In addition, the role of neurotensin in the modulation of autonomic regulatory input from the insula was investigated. The lateral hypothalamic area was surveyed for single units responding to electrical stimulation (500-900 microA, 0.5 Hz) of sites in the insular cortex from which cardiovascular pressor or depressor responses could be elicited. These units were tested for the influence of neurotensin on responses to stimulation of the insular cortex. Of 60 spontaneously firing neurons, 27 units responded to electrical stimulation of cardiovascular sites in the insula. Of the units responding to stimulation of cardiovascular sites in the insula, 14 units showed excitation only, 10 units showed excitation followed by inhibition and three units showed inhibition. Iontophoresis of 0.1-1.0 mM neurotensin (25-100 nA, pH 5.0-6.0) potentiated six of the excitatory responses and showed no effect on the inhibitory responses. In addition, nine neurons showed an increase in spontaneous activity with iontophoresis of neurotensin. Of these neurons, three were excited by insular stimulation and six did not respond. These findings indicate the likely origin of neurotensin in the lateral hypothalamic area and demonstrate that neurotensin has a role in the modulation of some of the cardiovascular regulatory input from the insular cortex.