Adaikkan Chinnakkaruppan, Joseph Justin, Foustoukos Georgios, Wang Jun, Polygalov Denis, Boehringer Roman, Middleton Steven J, Huang Arthur J Y, Tsai Li-Huei, McHugh Thomas J
Centre for Brain Research, Indian Institute of Science, Bengaluru, Karnataka, India.
Laboratory for Circuit and Behavioral Physiology, RIKEN Center for Brain Science, Wakoshi, Saitama, Japan.
Nat Commun. 2024 Mar 11;15(1):2190. doi: 10.1038/s41467-024-46478-3.
The precise temporal coordination of neural activity is crucial for brain function. In the hippocampus, this precision is reflected in the oscillatory rhythms observed in CA1. While it is known that a balance between excitatory and inhibitory activity is necessary to generate and maintain these oscillations, the differential contribution of feedforward and feedback inhibition remains ambiguous. Here we use conditional genetics to chronically silence CA1 pyramidal cell transmission, ablating the ability of these neurons to recruit feedback inhibition in the local circuit, while recording physiological activity in mice. We find that this intervention leads to local pathophysiological events, with ripple amplitude and intrinsic frequency becoming significantly larger and spatially triggered local population spikes locked to the trough of the theta oscillation appearing during movement. These phenotypes demonstrate that feedback inhibition is crucial in maintaining local sparsity of activation and reveal the key role of lateral inhibition in CA1 in shaping circuit function.
神经活动精确的时间协调对大脑功能至关重要。在海马体中，这种精确性体现在CA1区观察到的振荡节律中。虽然已知兴奋性和抑制性活动之间的平衡对于产生和维持这些振荡是必要的，但前馈抑制和反馈抑制的不同贡献仍不明确。在这里，我们使用条件遗传学方法长期沉默CA1锥体细胞的传递，消除这些神经元在局部回路中招募反馈抑制的能力，同时记录小鼠的生理活动。我们发现这种干预会导致局部病理生理事件，涟漪幅度和固有频率显著增大，并且在运动过程中出现与theta振荡波谷锁定的空间触发局部群体尖峰。这些表型表明反馈抑制对于维持局部激活稀疏性至关重要，并揭示了CA1区侧向抑制在塑造回路功能中的关键作用。
