Shortly thereafter, intracerebroventricular administration of an Oxt antagonist was shown to inhibit social recognition ( Engelmann et al., 1998) that was confirmed by knockouts of the Oxt ( Ferguson et al., 2000) and Oxtr ( Takayanagi et al., 2005) genes. Beginning in the mid-1980's, it was discovered that the Oxtr is distributed heterogeneously in the central nervous system, including in the hippocampus ( de Kloet et al., 1985 van Leeuwen et al., 1985). Oxytocin (Oxt) was originally found to regulate parturition ( Dale, 1906) and lactation ( Ott and Scott, 1910 Schafer and Mackenzie, 1911), acting through a single oxytocin receptor (Oxtr) in the uterus and breasts, respectively ( Kimura et al., 1992). 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. Distributions were analyzed within hippocampal layers and regions as well.
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. Most pyramidal cell neurons of CA2 and many in the CA3 express Oxtr. 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. It is important to understand which neurons in the mouse dorsal hippocampus might be activated during memory formation. 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. 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. Oxytocin, acting through the oxytocin receptor (Oxtr) in the periphery, is best known for its roles in regulating parturition and lactation. Section on Neural Gene Expression, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States.
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