Vasopressin Differentially Modulates Non-NMDA Receptors in Vasopressin and Oxytocin Neurons in the Supraoptic Nucleus

Abstract

Magnocellular neurons of the supraoptic nucleus release the neuropeptides oxytocin and vasopressin from their dendrites to regulate their synaptic inputs. This study aims to determine the cellular mechanism by which vasopressin modulates excitatory synaptic transmission. Presumably by electroporation through perforated patch, we were able to successfully introduce biocytin into cells in which we performed an electrophysiological study. This method enabled us to determine that roughly half of the recorded neurons were immunoreactive to oxytocin-associated neurophysin and showed two characteristic features: an inward rectification and a sustained outward rectification. The remaining half showed a linear voltage-current relationship and was immunoreactive to vasopressin-associated neurophysin. Using these electrophysiological characteristics and post hoc immunohistochemistry to identify vasopressin or oxytocin neurons, we found that vasopressin decreased evoked EPSCs in vasopressin neurons while increasing EPSCs in oxytocin neurons. In both types of neurons, EPSC decay constants were not affected, indicating that desensitization of non-NMDA receptors did not underlie the EPSC amplitude change. In vasopressin neurons, both vasopressin and a V1a receptor agonist, F-180, decreased AMPA-induced currents, an effect blocked by a V1a receptor antagonist SR49059. In oxytocin neurons, AMPA-induced currents were facilitated by vasopressin, whereas F-180 had no effect. An oxytocin receptor antagonist blocked the facilitatory effect of vasopressin. Thus, we conclude that vasopressin inhibits EPSCs in vasopressin neurons via postsynaptic V1a receptors, whereas it facilitates EPSCs in oxytocin neurons through oxytocin receptors.

Integration of Asynchronously Released Quanta Prolongs the Postsynaptic Spike Window

“…Likewise, vasopressin (VP) cells can release VP (Pow and Morris, 1989) or dynorphin (Watson et al, 1982). These molecules have all been shown previously to modulate neurotransmission in the PVN or supraoptic nucleus (Brussaard et al, 1996;Kombian et al, 1997;Hirasawa et al, 2003;Oliet et al, 2007). Although the vast majority of EPSCs recorded in MNCs displayed synchronous followed by asynchronous release, we did record EPSCs in some cells that displayed robust asynchronous release with little synchronous component.…”

GABAergic Excitation of Vasopressin Neurons

“…We examined GABA A receptor-mediated transmission in AVP neurons identified with electrophysiological characteristics 30,31 or post hoc immunohistochemical analysis. 30 In most of the identified AVP neurons, E GABA was negative to the action potential threshold (which was ≈−45 mV), and the GABA A receptor agonist muscimol decreased the firing rate by causing hyperpolarization. These findings indicate that GABA is inhibitory in most AVP neurons as has been reported in most previous studies.…”

“…Many of the putative AVP neurons, sampled from the SON or the lateral magnocellular subnucleus of the PVN, exhibited the electrophysiological characteristics of AVP neurons, 30,31 including phasic firing patterns ( Figure 1A), with little or no inward rectification at membrane potentials between −50 and −130 mV ( Figure 1B). After recordings, immunohistochemical analysis ( Figure 1C) confirmed that the cells that exhibited the physiological signature of AVP neurons did express AVP neurophysin (21 of 23 cells from 7 rats).…”

Vasopressin Inhibits Glutamate Release via Two Distinct Modes in the Brainstem

“…AVP, however, also has significant actions at central oxytocin receptors as well (Hirasawa et al, 2003). The V1a antagonist SR49059 possesses little activity at central oxytocin receptors (Manning et al, 1993).…”