催產素 (Oxytocin) 是一個含有九個胺基酸的胜肽荷爾蒙，由下視丘的視上核 (supraoptic nucleus) 及室旁核 (paraventricular nucleus) 所合成，其分泌後主要運送至腦垂體後葉進行儲存，其釋放至血液中會促進婦女在分娩時產生子宮收縮及產後促進乳汁分泌。此外其亦可作為神經傳導物質在大腦中作用，進而調控社交及非社交行為。催產素可以藉由活化催產素受體進而產生生理作用。催產素受體已被發現大量表現於海馬迴 CA2 區域中，而CA2 神經元的活性也被證實與社交記憶的形成有關。社交辨認記憶是動物用來區辨同種不同個體間差異的能力，其可能透過嗅覺系統分辨個體氣味，使動物在面臨抉擇時做出正確的應對。然而目前對催產素受體訊息如何在CA2 區域調控社交辨認記憶的表現目前尚未被完全了解清楚。先前我們實驗室利用病毒載體注射的方式局部剔除 CA2 區域催產素受體的實驗中證明了 CA2 催產素訊息對於長期社交辨認記憶形成的影響，但因無法排除 CA3a區域的角色，因此我們在此研究中採用 Amigo2-cre 專一性的來剔除 CA2 催產素受體的方式來探討其對於長期社交記憶形成的影響。在以催產素受體自發螢光的轉殖小鼠的實驗中，我們發現催產素受體主要表現在小鼠海馬迴 CA2 區域中。使用 Cre-loxP 重組酶 (recombinase) 系統將小鼠的 CA2 區域催產素受體專一性剔除的小鼠中，我們發現不論是公鼠或母鼠，七天的長期社交辨認記憶表現明顯受損，但社交能力、新奇性及短期社交辨認記憶並沒有受到影響。利用立體定位病毒注射技術及化學遺傳學的方法活化室旁核釋放催產素的細胞，增加內生性催產素的量釋放到 CA2 區域，我們發現小鼠社交能力、新奇性並未受到影響，且長期社交辨認記憶有些微的促進作用但未達統計意義。利用同樣的方法抑制背側 CA2 到腹側 CA1 的神經路徑，在社交能力、新奇性也沒有受到影響，而長期社交辨認記憶表現較差。綜合以上結果，我們發現催產素作用在 CA2 區域的催產素受體上，具有調控長期社交辨認記憶作用，CA2 神經元可能透過投射到腹側 CA1 的神經路徑來調控社交記憶的形成，此等研究證明了海馬迴 CA2 區域對於長期社交記憶形成中扮演了重要的角色。

Oxytocin (OXT) is a nonapeptide hormone that is synthesized and released from the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus. OXT was originally found to promote lactation and regulate parturition in the breasts and uterus. It also acts as neurotransmitter to modulate various of social and nonsocial behaviors. OXT binds to its OXT receptor (OXTRs) to exert its functions. OXTRs mainly expressed in hippocampal CA2 region, related to social memory processing. Social recognition memory (SRM) is the ability of animals to remember and recognize familiar or unfamiliar conspecifics. With this ability, animals can choose appropriate response according to different situations through the olfactory system. How CA2 OXTRs signaling modulates SRM formation remains unclear. Previously we found that OXTR signaling in CA2 is essential for long-term SRM formation, but cannot exclude the influence of CA3a. Thus, Amigo2-Cre mice crossed with OXTRf/f mice were used to explore the persistence of long-term SRM. We found strong OXTR expression in hippocampal CA2 pyramidal neurons in OXTR Venus-Neo/+ mice. By using cre recombinase to conditionally knockout CA2 oxtr, we found that both male and female mice showed deficits in long-term SRM. Then, stereotaxic viral injection and chemogenetic approaches were used to enhance endogenous OXT release to CA2 region. Activation of PVN OXT neurons partially promotes the generation of long-term SRM. Furthermore, inhibition of dCA2 to vCA1 circuit impaired the persistence of long-term SRM. Together, we found that OXT modulate long-term SRM by binding on CA2 OXTR and a circuit from dCA2 to vCA1 is crutial to regulate long-term SRM formation. This research indicated that hippocampal CA2 region plays an important role in the establishment of long-term SRM.

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