海马CA3区在学习和记忆中起着重要作用。CA3锥体神经元(PNs)接受两个突出的兴奋性输入-来自齿状回(DG)的苔藓纤维(MFs)和来自CA3PNs的复发性络脉(RCs)-在模式分离和模式完成中起相反的作用。分别。尽管海马解剖的背侧异质性,生理学,行为已经确立,关于CA3PN中突触连接的背侧异质性一无所知。在这项研究中,我们进行了Timm的硫化银染,树突和脊柱形态学分析,和两种性别的小鼠的离体电生理学,以研究沿着CA3背腹轴的MF和RC途径的异质性。我们的形态学分析表明,腹侧CA3(vCA3)PNs具有更大的树突长度和更复杂的树突树枝化,与背侧CA3(dCA3)PN相比。此外,使用ChannelRhodopsin2(ChR2)辅助膜片钳记录,我们发现,从dCA3到vCA3,RC-MF激发驱动到CA3PN的比率大幅增加,而vCA3PN接收的MF明显较弱,但是更强的RCs,激励比dCA3PNs。鉴于MF与RC输入在模式分离与完成中的不同作用,我们发现CA3PNs中MF和RC兴奋的显着背腹侧变化可能对CA3回路对海马功能的背腹侧差异的贡献具有重要的功能意义。意义陈述海马CA3区对于记忆形成是必需的。CA3锥体神经元接受来自CA3的复发性侧支(RC)和来自齿状回(DG)的苔藓纤维(MF),它们在模式完成(内存泛化)和分离(区分)方面具有相反的功能,分别。尽管海马背腹异质性已得到很好的证实,CA3连接的背腹侧异质性未知。这里,我们证明了RC-MF激励的比例从dCA3到vCA3大幅增加,vCA3接收显著较弱的MF,但是更强的RC,激发比dCA3。因此,我们的研究揭示了一种新的基于CA3的突触机制,该机制可能为腹侧海马体提供计算优势,使其更强烈地参与需要比背侧海马体更低精确度但更一般化的行为.
The hippocampal CA3 region plays an important role in learning and memory. CA3 pyramidal neurons (PNs) receive two prominent excitatory inputs-mossy fibers (MFs) from dentate gyrus (DG) and recurrent collaterals (RCs) from CA3 PNs-that play opposing roles in pattern separation and pattern completion, respectively. Although the
dorsoventral heterogeneity of the hippocampal anatomy, physiology, and behavior has been well established, nothing is known about the
dorsoventral heterogeneity of synaptic connectivity in CA3 PNs. In this study, we performed Timm\'s sulfide silver staining, dendritic and spine morphological analyses, and ex vivo electrophysiology in mice of both sexes to investigate the heterogeneity of MF and RC pathways along the CA3
dorsoventral axis. Our morphological analyses demonstrate that ventral CA3 (vCA3) PNs possess greater dendritic lengths and more complex dendritic arborization, compared with dorsal CA3 (dCA3) PNs. Moreover, using ChannelRhodopsin2 (ChR2)-assisted patch-clamp recording, we found that the ratio of the RC-to-MF excitatory drive onto CA3 PNs increases substantially from dCA3 to vCA3, with vCA3 PNs receiving significantly weaker MFs, but stronger RCs, excitation than dCA3 PNs. Given the distinct roles of MF versus RC inputs in pattern separation versus completion, our findings of the significant
dorsoventral variations of MF and RC excitation in CA3 PNs may have important functional implications for the contribution of CA3 circuit to the
dorsoventral difference in hippocampal function.