Oxytocin Excites Neurons Located in the Ventromedial Nucleus of the Guinea‐Pig Hypothalamus

Abstract

The area of the ventromedial nucleus of the hypothalamus in the guinea-pig was shown in autoradiographs to contain high affinity binding sites for oxytocin. In order to ascertain whether these sites may represent neuronal receptors, single-cell extracellular recordings were obtained from ventromedial neurons in coronal slices of t h e hypothalamus of adult guinea-pigs. Oxytocin applied in the nanomolar range excited about half of the neurons tested; none were inhibited. The response to the peptide was reversible and concentration-dependent. It was exerted directly since it persisted under t h e condition of synaptic isolation. Moreover, the effect was specific since it could be mimicked by a selective oxytocin agonist and since vasopressin was usually at least 10-fold weaker than oxytocin. These findings suggest that the binding sites for oxytocin detected by light microscopic autoradiography in the guinea-pig hypothalamic ventromedial nucleus represent functional receptors.In the rat brain, specific high affinity binding sites for oxytocin could be detected in various areas by light microscopic autoradiography, both in developing ( I ) and adult animals (2-5). In several of these areas, oxytoci?, was shown to excrt a neuronal effect ( I , 6 12), corroborating the view that binding sites detected by autoradiography represent, at least in part, functional receptors associated with neurons.Unexpectedly, when other species were examined, marked regional differences in the distribution of oxytocin binding sites were found ( 1 3). Thus, the ventral hippocampus and the dorsal motor nucleus of the vagus nerve were labelled in the rat but not in the guinea-pig (9, 11). In accordance with these autoradiographical data, electrophysiological recordings showed that neurons in the hippocampus and in the dorsal vagal nucleus of the rat were excited by oxytocin; in contrast, no neuronal sensitivity to this peptide was observed in the homologous area in the guinea-pig brain (9, 1 I).Amongst the regions of the rat brain which are most intensely labelled by [3H]oxytocin and by the radioiodinated selective oxytocin antagonist [1251]OTA (l4), is the hypothalamic ventromedial nucleus ( 1 , 4, 5). In the present study, we assessed whether the hypothalamic ventromedial nucleus also contains oxytocin binding sites in the guinea-pig. Moreover, in order to determine whether hypothalamic ventromedial neurons in this species are sensitive to oxytocin, we have carried out extracellular recordings from hypothalamic slices. The specificity of the neuronal action of oxytocin was ascertained by using a synthetic structural analogue, acting as a selective agonist (15). Part of these data have been presented a t scientific meetings (16,17).

Neuropeptide Signaling is Required to Implement a Line Attractor Encoding a Persistent Internal Behavioral State

“…Perfusing a mixture of 400nM (each) OXT plus AVP or individually administering these peptides elicited strong (ΔF/F ∼500-600%) responses in VMHvl Esr1 cells (Figure 1Fii and Supplemental Figure S1F-G). These findings demonstrated the presence of functional AVP and OXT receptors in VMHvl Esr1 neurons, consistent with prior electrophysiological studies in mice and guinea pigs 71,72 . Furthermore, it established a system for evaluating cellular responses to OXT and AVP following CRISPR/Cas9 based mutations of their receptors.…”

Ventromedial Hypothalamus and the Generation of Aggression

“…The oxytocin receptor is a Gq coupled receptor and expressed highly in the VMHvl (Young et al, 1997 ; Gould and Zingg, 2003 ) ( www.brain-map.org , experimental ID: 75081001). In vitro slice recording showed that oxytocin can directly excite VMHvl cells when bath applied (Inenaga et al, 1991 ). The source of oxytocin to the VMHvl is not clear.…”

The Role of Oxytocin Release in the Mediobasal Hypothalamus of the Sheep in Relation to Female Sexual Receptivity

“…The mediobasal hypothalamus (MBH) has been identified as an important site for the feedback action of sex steroids on sexual receptivity and the luteinizing hormone surge in both the rat (9) and the sheep (10). This brain region also contains OXY receptors in rodents (1 1,12), and OXY infusions into this site in rats stimulate both neuronal activity (13) and female sexual receptivity (5,7). Oestrogen treatment also increases the number of OXY receptors in the MBH (11).…”