Oxytocin Regulates Synaptic Transmission in the Sensory Cortices in a Developmentally Dynamic Manner

Abstract

The development and stabilization of neuronal circuits are critical to proper brain function. Synapses are the building blocks of neural circuits. Here we examine the effects of the neuropeptide oxytocin on synaptic transmission in L2/3 pyramidal neurons of the barrel field of the primary somatosensory cortex (S1BF). We find that perfusion of oxytocin onto acute brain slices significantly increases the frequency of miniature excitatory postsynaptic currents (mEPSC) of S1BF L2/3 pyramidal neurons at P10 and P14, but reduces it at the later ages of P22 and P28; the transition occurs at around P18. Since oxytocin expression is itself regulated by sensory experience, we also examine whether the effects of oxytocin on excitatory synaptic transmission correlate with that of sensory experience. We find that, indeed, the effects of sensory experience and oxytocin on excitatory synaptic transmission of L2/3 pyramidal neurons both peak at around P14 and plateau around P18, suggesting that they regulate a specific form of synaptic plasticity in L2/3 pyramidal neurons, with a sensitive/critical period ending around P18. Consistently, oxytocin receptor (Oxtr) expression in glutamatergic neurons of the upper layers of the cerebral cortex peaks around P14. By P28, however, Oxtr expression becomes more prominent in GABAergic neurons, especially somatostatin (SST) neurons. At P28, oxytocin perfusion increases inhibitory synaptic transmission and reduces excitatory synaptic transmission, effects that result in a net reduction of neuronal excitation, in contrast to increased excitation at P14. Using oxytocin knockout mice and Oxtr conditional knockout mice, we show that loss-of-function of oxytocin affects baseline excitatory synaptic transmission, while Oxtr is required for oxytocin-induced changes in excitatory synaptic transmission, at both P14 and P28. Together, these results demonstrate that oxytocin has complex and dynamic functions in regulating synaptic transmission in cortical L2/3 pyramidal neurons. These findings add to existing knowledge of the function of oxytocin in regulating neural circuit development and plasticity.

Robust GRK2/3/6-dependent desensitization of oxytocin receptor in neurons

“… 49 Furthermore, electrophysiological studies showed that OXTR activation causes varied effects in different neurons, which include postsynaptic transmission changes, spike generation, and presynaptic release modulation. 13 , 14 , 15 , 16 , 17 , 18 , 50 We inquired whether TGOT-induced spiking in LS neurons is derived from a cell autonomous effect on spike generation and/or caused by the presynaptic effect on neurotransmitter release. We further asked if the presynaptic and cell autonomous responses undergo similar desensitization.…”

The expansion of newborn neurons in hippocampus improves social recognition deficit in a mouse model of autism

“…Pan et al reported that the synaptic plasticity of the neural circuit in the hippocampus could also be improved by repeated administration of oxytocin (46). In addition, its possible that oxytocin modulates these processes indirectly by acting on oxytocin-responsive cells within brain regions that provide afferent input to the dentate gyrus such as the amygdala (47) or cortices (48), indicating that the oxytocin may act in multiple ways to induce the neurogenesis of DG.…”

Dynamic modulation of inhibition ability following repeated exposures to morphine in macaque monkey

“…Previous studies have indicated that oxytocin changes the turnover of dopamine or its D2R receptor affinity in nucleus accumbens (NAcc) and also inhibits the NAcc through activation of GABAergic interneurons (Dölen et al, 2013;Georgiou et al, 2015;Qi et al, 2008;Romero-Fernandez et al, 2013;Wang et al, 2018). These studies suggest that oxytocin might modulate neuroplasticity in dopaminergic mesocorticolimbic pathways and potentially interact with the effects of opioids on these neurocircuitries (Dölen et al, 2013;Rajamani et al, 2018;Zhang et al, 2021). However, our monkeys were transiently exposed to oxytocin about 21 months before the start of morphine administration; and therefore, it is highly unlikely that the previous exposure to oxytocin (which is a natural hormone) induced any long-lasting lingering effect to interfere with morphine effects in the current study.…”