A gamma‐aminobutyric‐acid‐mediated baroreceptor input to supraoptic vasopressin neurones in the rat.

Abstract

SUMMARY1. Extracellular recordings in pentobarbitone anaesthetized male Long-Evans rats examined the influence of electrical stimulation in the diagonal band of Broca on the excitability of 113 putative vasopressin-secreting and 22 putative oxytocinsecreting neurosecretory neurones in the hypothalamic supraoptic nucleus.2. Single pulse or repetitive (5-20 Hz) stimulation in the ventral part of the diagonal band evoked a prominent reduction in the excitability of83 % ofvasopressinsecreting neurones with no effect on the remainder. Amongst oxytocin-secreting neurones, 59 % were unresponsive, 27 % responded with an increase in activity while only 14 % revealed an inhibitory pattern similar to vasopressin-secreting neurones.3. Diagonal band stimulation-evoked inhibitions were reversibly abolished by local pressure applications of bicuculline methiodide (100 fM) to twenty out of twenty vasopressin-secreting cells tested, whereas strychnine sulphate (100 FtM) was without effect on four out of four cells tested. 4. In five out of five vasopressin-secreting cells tested, bicuculline applications reversibly abolished the reduction in their activity that follows peripheral baroreceptor activation. Failure to alter baroreflex-evoked depressions in firing during similar trials with prazosin hydrochloride (10 #M, six cells tested), timolol maleate (20 /tM, six cells tested) or strychnine sulphate (100 /M, three cells tested) indicated the specificity of bicuculline's action.5. These findings suggest that a GABAergic pathway from the diagonal band of Broca preferentially innervates vasopressin-secreting neurosecretory supraoptic nucleus (s.o.n.) neurones, and support the view that the baroreflex-induced depression in firing of s.o.n. vasopressin-secreting neurones is mediated in large part through this input.

GABAergic Excitation of Vasopressin Neurons

“…33 GABAergic afferents to AVP neurons mediate the reflexive inhibition of these cells by arterial baroreceptors. 15 In control rats (n=3), we found that the activation of baroreceptors by an intravenous injection of the α-adrenergic agonist phenylephrine (3-9 μg/kg body weight) resulted mostly in the inhibition of SON neurons (11 of 14 neurons; Figure 6A-6C, left panels). In contrast, in the DOCA-salt-treated rats (n=4), baroreceptor activation by phenylephrine mostly excited SON neurons (12 of 16 neurons; Figure 6A-6C, right panels).…”

“…They also respond to pressure increases by inhibiting the vasoconstrictive center of the medulla and suppressing the electric activity of AVP neurons through the release of GABA. 15 The resulting decreases in heart rate, cardiac contractility, and AVP release from the posterior pituitary, along with vasodilation, cause blood pressure to decrease. Using the systemic administration of phenylephrine to interrogate the baroreflex, we discovered that arterial baroreceptor activation led to the excitation, rather than inhibition, of SON neurons in DOCA-salt model rats.…”

“…[12][13][14][15][16][17][18] Recent work from our laboratory 19 indicated that GABA does not always function as an inhibitory neurotransmitter in this circuit. We demonstrated that, although GABA generally inhibits AVP neurons under resting conditions, it excites them under chronic hyperosmotic stress, a situation that demands increased AVP secretion.…”

Serotonergic mechanisms of the lateral parabrachial nucleus in renal and hormonal responses to isotonic blood volume expansion

“…This latter pathway, activated by volume load, relays arterial baroreceptor information to the VP neurons in the SON and includes the diagonal band of Broca (DBB) that projects to and activates GABAergic neurons in the PNZ. In turn, PNZ neurons release GABA into the SON, inhibiting VPergic neurons, and thereby inhibit VP release after blood volume expansion (21,22,31,49). Recent studies have shown that volume expansion increases c-Fos positive cells in the PNZ and DBB (20 -22, 30).…”

Symposium Proceedings

“…More precisely, electrophysiological studies have demonstrated that brief increases in blood pressure sufficient to activate peripheral baroreceptors evoke a selective GABAA receptor-mediated postsynaptic inhibition of VP neurones in SON (Jhamandas & Renaud, 1987). 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).…”