LATERAL HYPOTHALAMIC-LESIONS ALTER BARORECEPTOR-EVOKED INHIBITION OF RAT SUPRAOPTIC VASOPRESSIN NEURONS

1. Previous electrophysiological studies on rat hypothalamic supraoptic nucleus neurones have demonstrated that both the activation of peripheral baroreceptors (induced by a brief rise in arterial pressure consequent to an intravenous injection of an a-adrenergic agonist, metaraminol) and electrical stimulation in the diagonal band of Broca evokes a GABA-mediated postsynaptic inhibition which selectively involves the phasic-firing (putative vasopressin-secreting) neuronal population. Although baroreceptor-triggered inhibitions are abolished after diagonal band lesions, anatomical data support the hypothesis that the GABAergic neurones mediating both the baroreflex and electrically induced inhibitions are not located in the diagonal band, but rather in the lateral hypothalamus adjacent to the supraoptic nucleus. To determine the validity of this hypothesis, excitotoxic lesions were placed in the lateral hypothalamus and their effects on both baroreceptor- and diagonal band-evoked inhibitions were evaluated. 2. Male Long-Evans rats were initially anaesthetized with intraperitoneal pentobarbitone, stereotaxically injected with an excitotoxin (ibotenic acid) or vehicle into the lateral hypothalamus on the left side and allowed to recover. Three or more days later, animals were again anaesthetized with pentobarbitone and the ventral surface of their hypothalamus was exposed for electrophysiological recording of neurones in the left supraoptic nucleus. In all injected animals, extracellular recordings from antidromically identified, phasically firing supraoptic neurones were evaluated for their response to activation of peripheral baroreceptors and to electrical stimulation in the diagonal band. 3. Increases in arterial pressure sufficient to activate peripheral baroreceptors were achieved by intravenous bolus infusions of metaraminol (10 mug/10 mul). In vehicle control animals (n = 6), the activity of 34/39 neurones was inhibited by baroreceptor activation. In lesion control animals (n = 13) similar inhibitions were observed from 60/65 neurones. In the lateral hypothalamic lesioned group (n = 7), the activity of only 12/34 neurones were inhibited by similar elevations in blood pressure. 4. Ibotenic acid lesions in the lateral hypothalamus also disrupted the responsiveness of supraoptic neurones to electrical stimulation in the diagonal band. Whereas diagonal band stimulation in vehicle control and lesion control rats reduced the excitability in 7/9 cells and 15/19 cells respectively, only 1/7 cells responded in the lesioned animals. 5. Lesions having a significant effect on the responsiveness of vasopressin-secreting neurones to baroreceptor activation extended laterally towards the nucleus of the lateral olfactory tract, dorsally into the striatum and medially to the fornix. These lesions had little effect on the discharge properties of supraoptic neurones; the only detectable difference in the groups was a significant shortening in the mean latency for antidromic activation (12.7 +/- 0.5 ms) in the lesion group compared with vehicle control (15.5 +/- 0.5 ms; P < 0.01). 6. The diagonal band results contrast with those following stimulation in the median preoptic nucleus, where preliminary data indicate a direct GABAergic projection to supraoptic neurones. In lesioned animals where five tested neurones failed to respond to baroreceptor activation, four still displayed a median preoptic-evoked depressant response, implying that the lesions had not damaged fibres of passage. 7. These observations demonstrate the importance of local lateral hypothalamic neurones in a GABA-mediated inhibition of supraoptic nucleus vasopressin-secreting neurones consequent to activation of peripheral baroreceptors and electrical stimulation in the diagonal band. This supports the hypothesis that the GABAergic interneurones which mediate a baroreceptor-induced inhibition of supraoptic vasopressin-secreting neurones are not located in the diagonal band, but rather in an area of the lateral hypothalamus close to the target neurones.