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

1. Previous electrophysiological studies on rat hypothalamic supraopti c nucleus neurones have demonstrated that both the activation of perip heral baroreceptors (induced by a brief rise in arterial pressure cons equent to an intravenous injection of an a-adrenergic agonist, metaram inol) 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. A lthough baroreceptor-triggered inhibitions are abolished after diagona l band lesions, anatomical data support the hypothesis that the GABAer gic neurones mediating both the baroreflex and electrically induced in hibitions are not located in the diagonal band, but rather in the late ral hypothalamus adjacent to the supraoptic nucleus. To determine the validity of this hypothesis, excitotoxic lesions were placed in the la teral hypothalamus and their effects on both baroreceptor- and diagona l band-evoked inhibitions were evaluated. 2. Male Long-Evans rats were initially anaesthetized with intraperitoneal pentobarbitone, stereota xically injected with an excitotoxin (ibotenic acid) or vehicle into t he lateral hypothalamus on the left side and allowed to recover. Three or more days later, animals were again anaesthetized with pentobarbit one and the ventral surface of their hypothalamus was exposed for elec trophysiological 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 electr ical stimulation in the diagonal band. 3. Increases in arterial pressu re sufficient to activate peripheral baroreceptors were achieved by in travenous bolus infusions of metaraminol (10 mug/10 mul). In vehicle c ontrol animals (n = 6), the activity of 34/39 neurones was inhibited b y baroreceptor activation. In lesion control animals (n = 13) similar inhibitions were observed from 60/65 neurones. In the lateral hypothal amic lesioned group (n = 7), the activity of only 12/34 neurones were inhibited by similar elevations in blood pressure. 4. Ibotenic acid le sions in the lateral hypothalamus also disrupted the responsiveness of supraoptic neurones to electrical stimulation in the diagonal band. W hereas diagonal band stimulation in vehicle control and lesion control rats reduced the excitability in 7/9 cells and 15/19 cells respective ly, only 1/7 cells responded in the lesioned animals. 5. Lesions havin g a significant effect on the responsiveness of vasopressin-secreting neurones to baroreceptor activation extended laterally towards the nuc leus of the lateral olfactory tract, dorsally into the striatum and me dially 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 antidr omic activation (12.7 +/- 0.5 ms) in the lesion group compared with ve hicle control (15.5 +/- 0.5 ms; P < 0.01). 6. The diagonal band result s contrast with those following stimulation in the median preoptic nuc leus, where preliminary data indicate a direct GABAergic projection to supraoptic neurones. In lesioned animals where five tested neurones f ailed to respond to baroreceptor activation, four still displayed a me dian preoptic-evoked depressant response, implying that the lesions ha d 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 conseq uent to activation of peripheral baroreceptors and electrical stimulat ion in the diagonal band. This supports the hypothesis that the GABAer gic interneurones which mediate a baroreceptor-induced inhibition of s upraoptic vasopressin-secreting neurones are not located in the diagon al band, but rather in an area of the lateral hypothalamus close to th e target neurones.