一个分子定义的 CA3 递归环路调控网络动态与空间工作记忆
A molecularly defined recurrent CA3 circuit regulates network dynamics and spatial working memory
海马CA3区支持协调的网络活动和记忆过程，但分子上不同的CA3神经元群体如何参与回返环路功能仍知之甚少。在此，我们确定St18是深层、爆发性放电CA3锥体神经元中一个独特群体的分子标志物，并构建了St18-Cre小鼠品系以对其进行选择性遗传靶向。与经典CA3锥体神经元不同，St18神经元优先双侧支配CA3，仅向CA1发出稀疏投射。此外，St18神经元在内源性CA3尖波涟漪期间高度活跃，其光遗传学激活可在CA3而非CA1诱发局部涟漪样活动。进一步地，化学遗传学抑制显著减少CA3涟漪的发生，而不显著影响CA1涟漪的发生，并选择性损害空间工作记忆表现。总之，这些发现揭示了一个分子定义的CA3回返环路的功能意义，将神经元异质性与海马网络动力学及空间工作记忆联系起来。
用分子标记把 CA3 中一类深层爆发型锥体神经元单独标出并操纵，为区分局部环路与 CA1 输出提供了可借用的靶点。
The hippocampal CA3 region supports coordinated network activity and memory processes, but how molecularly distinct CA3 neuronal populations contribute to recurrent circuit function remains poorly understood. Here we identify St18 as a molecular marker of a distinct population of deep-layer, burst-firing CA3 pyramidal neurons and generate an St18-Cre mouse line for their selective genetic targeting. In contrast to canonical CA3 pyramidal neurons, St18 neurons preferentially innervate CA3 bilaterally, with only sparse projections to CA1. Moreover, St18 neurons are highly active during endogenous CA3 sharp-wave ripples, and their optogenetic activation evokes local ripple-like activity in CA3 but not in CA1. Furthermore, chemogenetic suppression markedly reduces CA3 ripple occurrence without significantly affecting CA1 ripple occurrence and selectively impairs spatial working memory performance. Together, these findings reveal the functional significance of a molecularly defined CA3 recurrent circuit, linking neuronal heterogeneity to hippocampal network dynamics and spatial working memory.
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来源：bioRxiv · Neuroscience · biorxiv.org