Oxytocin Increases Phasic and Tonic GABAergic Transmission in CA1 Region of Mouse Hippocampus

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 (Thr 4 ,Gly 7 -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 GABA A receptors (GABA A Rs) 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 GABA A Rs 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 Ca 2+ 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.

Oxytocin receptors excite lateral nucleus of central amygdala by phospholipase Cβ‐ and protein kinase C‐dependent depression of inwardly rectifying K+channels

“…2018), but up‐modulates L‐type Ca 2+ channels to excite CA1 GABAergic interneurons (Maniezzi et al . 2019). In ventral tegmental area and interfascicular nucleus of mouse midbrain, OXT increases neuronal excitability by activating a non‐selective cation channel and Na + –Ca 2+ exchanger (Tang et al .…”

“…Activation of OXTRs has been shown to increase neuronal excitability by distinct ionic mechanisms depending on neuronal types. In the hippocampus, activation of OXTRs inhibits KCNQ-based M channels to depolarize CA2 pyramidal neurons (Tirko et al 2018), but up-modulates L-type Ca 2+ channels to excite CA1 GABAergic interneurons (Maniezzi et al 2019). In ventral tegmental area and interfascicular nucleus of mouse midbrain, OXT increases neuronal excitability by activating a non-selective cation channel and Na + -Ca 2+ exchanger (Tang et al 2014).…”

Oxytocin Differentiated Effects According to the Administration Route in a Prenatal Valproic Acid-Induced Rat Model of Autism

“…We also have found that IN and less IP administered OXT improved short term memory in the Y maze, and that was correlated with a decline of oxidative stress status. OXT receptors are distributed abundantly in hippocampus and other brain regions involved in memory functions, suggesting OXT role in memory formation [ 74 ] and activation of hippocampal OXT receptors was showed to favor synaptic plasticity and transmission and suppressing neuronal background firing [ 75 , 76 , 77 ]. Several animals studies using IN OXT treatment in rodents with impaired hippocampal functioning or impaired memory have reported also positive effects [ 50 , 75 , 78 , 79 ].…”

Links Between the Neurobiology of Oxytocin and Human Musicality

“…The peptide can also act presynaptically to affect neurotransmitter secretion (Dölen et al, 2013 ; Bakos et al, 2018 ). Overall, from a physiological perspective, oxytocin influences cell viability, synaptic and structural plasticity in neurons (Bakos et al, 2018 ; Jurek and Neumann, 2018 ; Pekarek et al, 2020 ), and modulates the balance of excitatory and inhibitory activity in regions such as the cerebral cortex and hippocampus (e.g., Mitre et al, 2016 ; Grinevich and Stoop, 2018 ; Lin and Hsu, 2018 ; Lopatina et al, 2018 ; Tirko et al, 2018 ; Cilz et al, 2019 ; Maniezzi et al, 2019 ; Tan et al, 2019 ), amygdala (Crane et al, 2020 ), and nucleus accumbens (Moaddab et al, 2015 ; Cox et al, 2017 ). Rodents lacking oxytocin or OXTR display impaired sociability and social memory (Ferguson et al, 2000 ).…”