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.

Highlights

  • 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)

  • The Cck+/Oxtr+ pyramidal cell layer (PCL) neurons in fasciola cinereum (FC), CA2, or CA3 were not included in our counts

  • CCK only neurons were not counted in the FC, CA2, or CA3 PCL neurons

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Summary

Introduction

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). Virally targeted expression of Cre recombinase to the hilar region of the dentate gyrus to eliminate the Oxtr there leads to reduced social discrimination as did elimination of Oxtr in the dorsal CA2 and immediately adjacent CA3 (Raam et al, 2017). Another study targeting those latter same neurons showed reduced long-term social memory (Lin et al, 2018). A recent review delves into these and similar studies in further detail (Cilz et al, 2019)

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