A Distributed Network for Social Cognition Enriched for Oxytocin Receptors

Abstract

Oxytocin is a neuropeptide important for social behaviors such as maternal care and parent-infant bonding. It is believed that oxytocin receptor signaling in the brain is critical for these behaviors, but it is unknown precisely when and where oxytocin receptors are expressed or which neural circuits are directly sensitive to oxytocin. To overcome this challenge, we generated specific antibodies to the mouse oxytocin receptor and examined receptor expression throughout the brain. We identified a distributed network of female mouse brain regions for maternal behaviors that are especially enriched for oxytocin receptors, including the piriform cortex, the left auditory cortex, and CA2 of the hippocampus. Electron microscopic analysis of the cerebral cortex revealed that oxytocin receptors were mainly expressed at synapses, as well as on axons and glial processes. Functionally, oxytocin transiently reduced synaptic inhibition in multiple brain regions and enabled long-term synaptic plasticity in the auditory cortex. Thus modulation of inhibition may be a general mechanism by which oxytocin can act throughout the brain to regulate parental behaviors and social cognition.

Oxytocin in the medial prefrontal cortex attenuates anxiety: Anatomical and receptor specificity and mechanism of action

“…OTR are located in the mPFC (Duchemin et al, 2017; Gould and Zingg, 2003; Insel and Shapiro, 1992; Liu et al, 2005; Mak et al, 2012; Mitre et al, 2016; Nakajima et al, 2014; Smeltzer et al, 2006) although little is known about subregional differences in OTR density which may be another factor contributing to the observed behavioral variations across mPFC subregions. Nonetheless, it is reasonable to assume that within the PL mPFC, OT reduces anxiety by acting on the OTR.…”

“…Oxytocin receptors (OTR) are expressed in the mPFC (Gould and Zingg, 2003; Insel and Shapiro, 1992; Liu et al, 2005; Mitre et al, 2016; Smeltzer et al, 2006) and so it is reasonable to assume that OT in the PL mPFC reduces anxiety by activating the OTR. However, receptors for the structurally similar neuropeptide, vasopressin (AVP), are also found in the mPFC (Kozorovitskiy et al, 2006; Smeltzer et al, 2006).…”

C-tactile afferents: Cutaneous mediators of oxytocin release during affiliative tactile interactions?

“…Oxytocin receptors are widely distributed throughout the brain, with dense representation within limbic forebrain regions where they co-localise with the classical neurotransmitters, allowing for oxytocin mediated modulation of a range of motivational and affective states and processes (Kendrick et al, 1997;Lee et al, 2009;Mitre et al, 2016).…”

“…Magnocellular oxytocin neurons of the PVN and SON project to the posterior pituitary from where oxytocin enters the circulation to induce numerous peripheral effects, including its involvement in lactation and parturition . Oxytocin receptors have also been identified throughout the central nervous system (CNS) and it is here, primarily through site specific interactions with the ascending monoamine systems, as well as with other neuropeptides, it facilitates a range of sensory and psychological processes essential for adaptive social behaviour, such as pair bonding and attachment formation Liu and Wang, 2003;Mitre et al, 2016;Yoshida et al, 2009). …”

Oxytocin Modulation of Neural Circuits

“…Recently, our group generated novel antibodies (OXTR-2) with high specificity for the mouse oxytocin receptor (Marlin et al 2015; Mitre et al 2016), which were used to characterize oxytocin receptor expression throughout the mouse brain in virgin females, mothers, and males (Fig. 1).…”