Oxytocin via oxytocin receptor excites neurons in the endopiriform nucleus of juvenile mice

The neuropeptide oxytocin (OXT) modulates social behaviors across species and may play a developmental role for these behaviors and their mediating neural pathways. Despite having high, stable levels of OXT receptor (OXTR) ligand binding from birth, endopiriform nucleus (EPN) remains understudied. EPN integrates olfactory and gustatory input and has bilateral connections with several limbic areas. Because the role of OXTR signaling in EPN is unknown, we sought to provide anatomical and electrophysiological information about OXTR signaling in mouse EPN neurons. Using in situ hybridization, we found that most EPN neurons co-express Oxtr mRNA and the marker for VGLUT1 and are thus glutamatergic cells. Based on high levels of OXTR ligand binding in EPN, we hypothesized that oxytocin application would modulate activity in these cells as measured by whole-cell patch-clamp electrophysiology. Bath application of OXT and an OXTR specific ligand (TGOT) increased the excitability of EPN neurons in wild-type, but not in OXTR-knockout tissue. These results show an effect of OXT on a presumably glutamatergic cell population within EPN. Given the robust, relatively stable OXTR expression in EPN throughout life, OXTR in this multi-sensory and limbic integration area may be important for modulating activity in response to an array of social or other salient stimuli throughout the lifespan and warrants further study. Significance statement There is a high level of oxytocin receptor (OXTR) expression in the mouse endopiriform nucleus (EPN) throughout development, however little is known about the effect of oxytocin on these neurons. We show here that Oxtr mRNA co-expresses mainly with VGLUT1, a glutamatergic cell marker. Using OXTR-EGFP mice to identify EPN, we show that OXT has a mainly excitatory effect on EPN neurons. Thus, activity in EPN neurons may be modulated by OXT during exposure to salient or social stimuli throughout development and this could affect development of behavioral responses during social exposure.