Ahmadi Siavash, Sasaki Takuya, Sabariego Marta, Leibold Christian, Leutgeb Stefan, Leutgeb Jill K
Neurobiology Department, School of Biological Sciences, University of California, San Diego, CA, USA.
Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Nat Commun. 2025 Jan 2;16(1):13. doi: 10.1038/s41467-024-54943-2.
The hippocampal CA3 subregion is a densely connected recurrent circuit that supports memory by generating and storing sequential neuronal activity patterns that reflect recent experience. While theta phase precession is thought to be critical for generating sequential activity during memory encoding, the circuit mechanisms that support this computation across hippocampal subregions are unknown. By analyzing CA3 network activity in the absence of each of its theta-modulated external excitatory inputs, we show necessary and unique contributions of the dentate gyrus (DG) and the medial entorhinal cortex (MEC) to phase precession. DG inputs are essential for preferential spiking of CA3 cells during late theta phases and for organizing the temporal order of neuronal firing, while MEC inputs sharpen the temporal precision throughout the theta cycle. A computational model that accounts for empirical findings suggests that the unique contribution of DG inputs to theta-related spike timing is supported by targeting precisely timed inhibitory oscillations. Our results thus identify a novel and unique functional role of the DG for sequence coding in the CA3 circuit.
海马体CA3亚区是一个高度连接的循环回路，通过生成和存储反映近期经历的连续神经元活动模式来支持记忆。虽然θ相位进动被认为在记忆编码过程中对生成连续活动至关重要，但支持跨海马亚区进行这种计算的电路机制尚不清楚。通过分析在没有其每个θ调制的外部兴奋性输入的情况下CA3网络活动，我们展示了齿状回（DG）和内侧内嗅皮层（MEC）对相位进动的必要且独特的贡献。DG输入对于CA3细胞在θ后期的优先放电以及组织神经元放电的时间顺序至关重要，而MEC输入则在整个θ周期中提高时间精度。一个解释实证结果的计算模型表明，DG输入对与θ相关的尖峰时间的独特贡献是由精确计时的抑制性振荡靶向支持的。因此，我们的结果确定了DG在CA3回路序列编码中的一种新颖且独特的功能作用。
