Hippocampal oxytocin receptors are necessary for discrimination of social stimuli

Abstract

Oxytocin receptor (Oxtr) signaling in neural circuits mediating discrimination of social stimuli and affiliation or avoidance behavior is thought to guide social recognition. Remarkably, the physiological functions of Oxtrs in the hippocampus are not known. Here we demonstrate using genetic and pharmacological approaches that Oxtrs in the anterior dentate gyrus (aDG) and anterior CA2/CA3 (aCA2/CA3) of mice are necessary for discrimination of social, but not non-social, stimuli. Further, Oxtrs in aCA2/CA3 neurons recruit a population-based coding mechanism to mediate social stimuli discrimination. Optogenetic terminal-specific attenuation revealed a critical role for aCA2/CA3 outputs to posterior CA1 for discrimination of social stimuli. In contrast, aCA2/CA3 projections to aCA1 mediate discrimination of non-social stimuli. These studies identify a role for an aDG-CA2/CA3 axis of Oxtr expressing cells in discrimination of social stimuli and delineate a pathway relaying social memory computations in the anterior hippocampus to the posterior hippocampus to guide social recognition.

Oxytocin and vasopressin in the rodent hippocampus

“…Optogenetic inhibition of ventral but not rostral dorsal CA1 cell bodies impairs the ability of male mice to recognize familiar conspecifics in both social discrimination and resident‐intruder paradigms . The ventral CA1 region receives input from the dorsal CA2 region and optical inhibition of terminals derived from the dorsal CA2/CA3 area in the caudal dorsal CA1 region reduces the social discrimination score of male subject mice compared to control animals . However, modest levels of social discrimination persist with inhibition of dorsal CA2/CA3 inputs to caudal dorsal CA1, which the authors suggest may be due to insufficient illumination or incomplete inhibition .…”

“…The ventral CA1 region receives input from the dorsal CA2 region and optical inhibition of terminals derived from the dorsal CA2/CA3 area in the caudal dorsal CA1 region reduces the social discrimination score of male subject mice compared to control animals . However, modest levels of social discrimination persist with inhibition of dorsal CA2/CA3 inputs to caudal dorsal CA1, which the authors suggest may be due to insufficient illumination or incomplete inhibition . Chemogenetic silencing of dorsal CA2 inputs to the ventral CA1 via local infusions of clozapine‐n‐oxide robustly impairs social memory, further supporting a dorsal CA2 to ventral CA1 circuit underlying social memory.…”

“…The Oxtr is not likely confined to one interneuron subtype. Multiplex ISH in the DG of mice suggests that Oxtr colocalizes with both somatostatin‐ and parvalbumin (PV)‐positive interneurons, as well as other Gad1‐positive neurons . Immunostaining finds Oxtr‐Venus colocalizes with both PV‐ and calretinin‐positive interneurons in mice .…”

The osmoresponsiveness of oxytocin and vasopressin neurones: Mechanisms, allostasis and evolution

“…Although all magnocellular neurones project to the posterior pituitary, subpopulations project to various central sites including the nucleus accumbens, hippocampus, amygdala and bed nucleus of the stria terminalis. [179][180][181][182][183][184] Vasopressin and oxytocin are released not only from nerve terminals in response to spike activity, but also from the soma and dendrites in response to the mobilisation of intracellular Ca 2+ . It is likely that, within the brain, oxytocin cells release not only glutamate at synapses in the manner typical of neurotransmitters, but also occasional vesicles containing oxytocin from axonal varicosities to act as a local neuromodulator.…”

Oxytocin and Rodent Models of Addiction

“…It is hypothesized this alteration in hippocampal excitability may, in turn, influence regions in the MCL circuit, such as the NAc and PFC, thereby mediating drug-induced neuroplasticity (Sarnyai & Kovacs, 2014). A recent study has also established that oxytocin receptors within the hippocampus (notably the anterior dentate gyrus, and anterior CA2/CA3) of mice are necessary for social stimuli discrimination and social recognition (Raam, McAvoy, Besnard, Veenema, & Sahay, 2017). It is possible, therefore, that prosocial memories, mediated by oxytocin in the hippocampus, inhibit the drug-related neuroplasticity, or alter the engrams associated with drug cues and reward.…”