Lateral hypothalamic lesions alter baroreceptor‐evoked inhibition of rat supraoptic vasopressin neurones.

Abstract

SUMMARY1. 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,g/10 l1). 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 MS 1877 R. NISSEN, J. T. CUNNINGHAM AND L. P. RENA UD 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 vasopressinsecreting 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 ...

GABA Is Excitatory in Adult Vasopressinergic Neuroendocrine Cells

“…The SON and PVN receive inputs from local glutamatergic interneurons located within the PVN (Daftary et al, 2000) and from glutamatergic and GABAergic interneurons in peri-nuclear regions (Boudaba et al, 1997; Wuarin, 1997), all of which may have a negative E GABA . Indeed, anatomical and electrophysiological studies suggest that afferent projections from the diagonal band of Broca and the median preoptic nucleus, structures that inhibit vasopressin release (Jhamandas and Renaud, 1986; Nissen and Renaud, 1994), relay through inhibitory interneurons proximal to the SON (Hatton et al, 1983; Tribollet et al, 1985; Jhamandas et al, 1989; Nissen et al, 1993). Finally, previous studies with GABA agonists often used relatively high concentrations of exogenous agonist (Ludwig and Leng, 2000), which, based on our findings, should cause a robust membrane depolarization and could lead to the suppression of firing due to sodium channel inactivation.…”

GABA receptor mediation of median preoptic nucleus‐evoked inhibition of supraoptic neurosecretory neurones in rat.

“…For example, stimulation in the diagonal band of Broca evokes a GABA-mediated inhibition of supraoptic neurones, but these are preferentially directed towards vasopressinsecreting cells (Jhamandas & Renaud, 1986). In addition, this inhibition appears to be mediated through GABAergic interneurones located in the perinuclear region adjacent to the supraoptic nucleus since excitotoxic destruction of this perinuclear region selectively disrupts the diagonal bandevoked inhibition without affecting MnPO-evoked inhibition (Nissen, Cunningham & Renaud, 1993). Interestingly, the responses of oxytocin-secreting neurones to electrical stimulation in MnPO appear to vary with stimulation frequency, with excitation at frequencies under 5 Hz and depression at higher frequencies.…”

Symposium Proceedings

“…Diagonal band of Broca neurones participate in a central pathway transducing this depressant effect (Jhamandas & Renaud, 1986;Cunningham et al 1992). Anatomical evidence suggesting that they do not influence SON cells directly but act through GABAergic interneurones located in a SON perinuclear zone (Jhamandas et al 1989) have been recently supported by the observation that lateral hypothalamic lesions by ibotenic acid alter baroreceptor-evoked inhibition of SON-VP neurones (Nissen et al 1993). Using the technique of microdialysis, we have been able to detect increases in extracellular GABA levels in the SON of anaesthetized rats following activation of baroreceptors (Voisin et al 1994b).…”