Characterization of Oxytocin Receptor Expression Within Various Neuronal Populations of the Mouse Dorsal Hippocampus

Abstract

Oxytocin, acting through the oxytocin receptor (Oxtr) in the periphery, is best known for its roles in regulating parturition and lactation. However, it is also now known to possess a number of important social functions within the central nervous system, including social preference, memory and aggression, that vary to different degrees in different species. The Oxtr is found in both excitatory and inhibitory neurons within the brain and research is focusing on how, for example, activation of the receptor in interneurons can enhance the signal-to-noise of neuronal transmission. It is important to understand which neurons in the mouse dorsal hippocampus might be activated during memory formation. Therefore, we examined the colocalization of transcripts in over 5,000 neurons for Oxtr with those for nine different markers often found in interneurons using hairpin chain reaction in situ hybridization on hippocampal sections. Most pyramidal cell neurons of CA2 and many in the CA3 express Oxtr. Outside of those excitatory neurons, over 90% of Oxtr-expressing neurons co-express glutamic acid decarboxylase-1 (Gad-1) with progressively decreasing numbers of co-expressing cholecystokinin, somatostatin, parvalbumin, neuronal nitric oxide synthase, the serotonin 3a receptor, the vesicular glutamate transporter 3, calbindin 2 (calretinin), and vasoactive intestinal polypeptide neurons. Distributions were analyzed within hippocampal layers and regions as well. These findings indicate that Oxtr activation will modulate the activity of ∼30% of the Gad-1 interneurons and the majority of the diverse population of those, mostly, interneuron types specifically examined in the mouse hippocampus.

Oxytocin administration in neonates shapes the hippocampal circuitry and restores social behavior in a mouse model of autism

“…In the anterior adult hippocampus OXTRs are expressed in pyramidal cells of aCA2/CA3d region and mainly in SST and/or PV interneurons of aCA2/CA3d and aDG (23, 27). In Magel2- KO adult mice, the number of SST+ cells was higher than in WT mice in both aCA2/CA3d (more 60%) and aDG (more 80%) regions (Figure 5 A-F and M-N).…”

“…In the anterior adult hippocampus OXTRs are expressed in pyramidal cells and in SST and/or PV interneurons of aCA2/CA3d region and in interneurons of aDG (see above, (12,16)). In control mice following social memory test, cFos expression was detected in 23 or 30% of SSTimmunopositive cells (SST+) and 22 or 28% of PV+ cells in the aCA2/CA3d or aDG regions following the social memory test, respectively ( Figure 6-figure supplement 1), suggesting an involvement of those interneurons in social memory.…”

“…In the aCA2/CA3d region, OXTRs are expressed in glutamatergic pyramidal neurons (which are also CCK positive) and in GABAergic interneurons, which account for over 90% of OXTR positive cells in the hippocampus (16). Notably, both types of neuron are necessary for the formation of stronger synapses that mediate LTP and social memory (12,13).…”

“…With regard to social memory, a critical role has been ascribed to hippocampal OXTR expression in the anterior dentate gyrus (aDG) hilar and anterior CA2/CA3distal regions (aCA2/CA3d) (23–26). In the aCA2/CA3d region, OXTRs are expressed in glutamatergic pyramidal neurons and in GABAergic interneurons, which account for over 90% of OXTR positive cells in the hippocampus (27). Notably, both types of neuron are necessary for the formation of stronger synapses that mediate long term potentiation and social memory (23, 24, 28).…”

Links Between the Neurobiology of Oxytocin and Human Musicality

“…Nonetheless, there are potential sites of interaction in some brain regions (Smith et al, 2019 ), and there is evidence of functionally relevant spillover of oxytocin into the extracellular space beyond traditional synaptic sites (Busnelli and Chini, 2017 ; Chini et al, 2017 ; Song and Albers, 2018 ). OXTRs are widely distributed and found in many neuronal types, expressed on cell bodies, dendrites, and axon terminals, and the receptor is also expressed by astrocytes (Wang et al, 2017 ; Bakos et al, 2018 ; Young and Song, 2020 ). In different species, the receptor seems to be specifically enriched in those sensory/perceptual systems that are most relevant to conspecific maternal as well as more general socially interactive behaviors (Grinevich and Stoop, 2018 ; Pekarek et al, 2020 ).…”