Journal
JOURNAL OF BIOMEDICAL SCIENCE
Volume 29, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s12929-022-00834-x
Keywords
Oxytocin; Oxytocin receptor; Social recognition memory; CA2; Hippocampus; Paraventricular nucleus
Categories
Funding
- National Health Research Institute [NHRI-EX110-10912NI, NHRI-EX111-10912NI]
- Ministry of Science and Technology [107-2320-B-006-037-MY3, 109-2320-B-006-039-MY3, 110-2331-B-006-036-MY3]
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This study reveals the crucial role of oxytocin receptor signaling in the dorsal hippocampus CA2 region in governing the persistence of long-term social recognition memory (SRM). By investigating the neural circuitry involved, the researchers identify the connection from dorsal CA2 to ventral CA1 as necessary for the formation of long-term SRM.
Background Social recognition memory (SRM) is the ability to distinguish familiar from novel conspecifics and is crucial for survival and reproductive success across social species. We previously reported that oxytocin (OXT) receptor (OXTR) signaling in the CA2/CA3a of dorsal hippocampus is essential to promote the persistence of long-term SRM, yet how the endogenous OXT system influences CA2 outputs to regulate long-term SRM formation remains unclear. Methods To achieve a selective deletion of CA2 OXTRs, we crossed Amigo2-Cre mice with Oxtr-floxed mice to generate CA2-specific Oxtr conditional knockout (Oxtr(-/-)) mice. A three-chamber paradigm test was used for studying SRM in mice. Chemogenetic and optogenetic targeting strategies were employed to manipulate neuronal activity. Results We show that selective ablation of Oxtr in the CA2 suffices to impair the persistence of long-term SRM but has no effect on sociability and social novelty preference in the three-chamber paradigm test. We find that cell-type specific activation of OXT neurons within the hypothalamic paraventricular nucleus enhances long-term SRM and this enhancement is blocked by local application of OXTR antagonist L-368,899 into dorsal hippocampal CA2 (dCA2) region. In addition, chemogenetic neuronal silencing in dCA2 demonstrated that neuronal activity is essential for forming long-term SRM. Moreover, chemogenetic terminal-specific inactivation reveals a crucial role for dCA2 outputs to ventral CA1 (vCA1), but not dorsal lateral septum, in long-term SRM. Finally, targeted activation of the dCA2-to-vCA1 circuit effectively ameliorates long-term SRM deficit observed in Oxtr(-/-) mice. Conclusions These findings highlight the importance of hippocampal CA2 OXTR signaling in governing the persistence of long-term SRM and identify a hippocampal circuit linking dCA2 to vCA1 necessary for controlling long-term SRM formation.
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