Abstract
Oxytocin is a neuropeptide that plays important peripheral and central neuromodulatory functions. Our data show that, following activation of oxytocin receptors (OtRs) with the selective agonist TGOT (Thr4,Gly7-oxytocin), a significant increase in frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSC) occurred in hippocampal CA1 pyramidal neurons (PYR) in mice. TGOT affected also sIPSC deactivation kinetics, suggesting the involvement of perisynaptic GABAA receptors (GABAARs) as well. By contrast, TGOT did not cause significant changes in frequency, amplitude or deactivation kinetics of miniature IPSC, suggesting that the effects elicited by the agonist are strictly dependent on the firing activity of presynaptic neurons. Moreover, TGOT was able to modulate tonic GABAergic current mediated by extrasynaptic GABAARs expressed by PYRs. Consistently, at spike threshold TGOT induced in most PYRs a significant membrane hyperpolarization and a decrease in firing rate. The source of increased inhibition onto PYRs was represented by stuttering fast-spiking GABAergic interneurons (INs) that directly respond to TGOT with a depolarization and an increase in their firing rate. One putative ionic mechanism underlying this effect could be represented by OtR activation-induced up-modulation of L-type Ca2+ channels. In conclusion, our results indicate that oxytocin can influence the activity of a subclass of hippocampal GABAergic INs and therefore regulate the operational modes of the downstream PYRs by increasing phasic and tonic GABAergic transmission in CA1 region of mouse hippocampus.
Highlights
Oxytocin (OT) is a small neuropeptide that plays important peripheral and central neuromodulatory functions
GABAergic spontaneous inhibitory postsynaptic currents (sIPSC) were whole-cell recorded from visually identified pyramidal neurons (PYR) positioned in CA1 stratum pyramidale of hippocampal brain slices from P17-P26 Otr+/+ mice and visualized by infrared microscopy
Spontaneous inhibitory postsynaptic currents were recorded from 23 PYRs in Otr+/+ mice during application of gap free voltage-clamp recordings and maintaining a holding potential of 0 mV, in the presence of 10 μM NBQX and 30 μM CPP to block glutamatergic synaptic inputs. sIPSC interevent intervals were exponentially distributed (Figure 1A) whereas sIPSC amplitudes were distributed lognormally (Figure 1B)
Summary
Oxytocin (OT) is a small neuropeptide that plays important peripheral (i.e., parturition and lactation) and central neuromodulatory functions. OT is mostly synthesized in the magnocellular neurons of the supraoptic nuclei and paraventricular nuclei of the hypothalamus, projecting to the posterior pituitary gland, where it is released into the bloodstream to exert its peripheral effects. Effects of Oxytocin on GABAergic Transmission in Hippocampus to several distinct brain regions (Ludwig and Pittman, 2003) where it operates as a neuromodulator (Raggenbass, 2001). Several electrophysiological studies have shown that OT is able to exert direct effects on specific neuronal populations in the CA1 area of the rat (Mühlethaler et al, 1983; Mühlethaler et al, 1984; Raggenbass et al, 1989; Raggenbass, 2001). OT seems to exert an excitatory action on a specific class of CA1 GABAergic interneurons (INs) and in turn to enhance inhibitory synaptic transmission onto CA1 pyramidal neurons (PYR) in rats (Zaninetti and Raggenbass, 2000; Owen et al, 2013)
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