The lateral septal area is rich in vasopressin V(1A) receptors and is densely innervated by vasopressinergic axons, originating mainly from the bed nucleus of the stria terminalis and the amygdala. Genetic and behavioral studies provide evidence that activation of vasopressin receptors in this area plays a determinant role in promoting social recognition. What could be the neuronal mechanism underlying this effect? Using rat brain slices and whole-cell recordings, we found that lateral septal neurons are under the influence of a basal GABAergic inhibitory input. Vasopressin, acting via V(1A) but not V(1B) receptors, greatly enhanced this input in nearly all neurons. The peptide had no effect on miniature inhibitory postsynaptic currents, indicating that it acted on receptors located in the somatodendritic membrane, rather than on axon terminals, of GABAergic interneurons. Cell-attached recordings showed that vasopressin can cause a direct excitation of a subpopulation of lateral septal neurons by acting via V(1A) but not V(1B) receptors. The presence in the lateral septum of V(1A) but not of V(1B) receptors was confirmed by competition binding studies using light microscopic autoradiography. In conclusion, vasopressin appears to act in the lateral septum in a dual mode: (i) by causing a direct excitation of a subpopulation of neurons, and (ii) by causing an indirect inhibition of virtually all lateral septal neurons. This modulation by vasopressin of the lateral septal circuitry may be part of the neuronal mechanism by which the peptide, acting via V(1A) receptors, promotes social recognition.

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The hypoglossal nucleus of young rats contains vasopressin binding sites and vasopressin can directly excite hypoglossal motoneurons. In addition, indirect evidence suggests that vasopressin can enhance the synaptic input to motoneurons. We have characterized this latter effect by using brainstem slices and whole-cell recordings. We found that, in the presence of blockers of fast glutamatergic transmission, vasopressin strongly facilitated inhibitory synaptic activity. On average, vasopressin caused a six-fold increase in the frequency and a 1.5-fold increase in the amplitude of GABAergic postsynaptic currents. The effect of vasopressin on glycinergic postsynaptic currents was similar in magnitude. Vasopressin did not affect the frequency of GABAergic or glycinergic miniature postsynaptic currents, indicating that the peptide-induced facilitation of inhibitory transmission was mediated by receptors located on the somatodendritic region rather than on axon terminals of presynaptic neurons. The pharmacological profile of these receptors was determined by using d[Cha4]AVP and dVDAVP, selective agonists of V1b and V2 vasopressin receptors, respectively, and Phaa-D-Tyr-(Et)-Phe-Gln-Pro-Arg-Arg-NH2, a selective antagonist of V1a vasopressin receptors. The two agonists had no effect on the frequency of inhibitory postsynaptic currents. By contrast, the antagonist suppressed the vasopressin-induced facilitation of these currents, indicating that the receptors involved were exclusively of the V1a type. Thus, vasopressin exerts a dual action on hypoglossal motoneurons: a direct excitatory action and an indirect action mediated by GABAergic and glycinergic synapses. By virtue of this dual effect, vasopressin could alter the input-output properties of these motoneurons. Alternatively, it could play a role in generating or modulating specific motor patterns.

As a hormone, vasopressin binds to three distinct receptors: V1a and V1b receptors, which induce phospholipase-Cbeta (PLCbeta) activation and Ca2+ mobilization; and V2 receptors, which are coupled to adenylyl cyclase. V1a and V1b receptors are also present in neurons. In particular, hypoglossal (XII) and facial (VII) motoneurons are excited following vasopressin-V1a receptor binding. The aim of the present study was double: (i) to determine whether V1b receptors contribute to the excitatory effect of vasopressin in XII and VII motoneurons; and (ii) to establish whether the action of vasopressin on motoneurons is mediated by Ca2+ signalling. Patch-clamp recordings were performed in brainstem slices of young rats. Vasopressin depolarized the membrane or generated an inward current. By contrast, [1-deamino-4-cyclohexylalanine] arginine vasopressin (d[Cha4]AVP), a V1b agonist, had no effect. The action of vasopressin was suppressed by Phaa-D-Tyr(Et)-Phe-Gln-Asn-Lys-Pro-Arg-NH2, a V1a antagonist, but not by SSR149415, a V1b antagonist. Thus, the vasopressin-induced excitation of brainstem motoneurons was exclusively mediated by V1a receptors. Light microscopic autoradiography failed to detect V1b binding sites in the facial nucleus. In motoneurons loaded with GTP-gamma-S, a non-hydrolysable analogue of GTP, the effect of vasopressin was suppressed, indicating that neuronal V1a receptors are G-protein-coupled. Intracellular Ca2+ chelation suppressed a Ca2+-activated potassium current, but did not affect the vasopressin-evoked current. H7 and GF109203, inhibitors of protein kinase C, were without effect on the vasopressin-induced excitation. U73122 and D609, PLCbeta inhibitors, were also without effect. Thus, excitation of brainstem motoneurons by V1a receptor activation is probably mediated by a second messenger distinct from that associated with peripheral V1a receptors.