Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709.
Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709
Proc Natl Acad Sci U S A. 2018 Feb 20;115(8):E1886-E1895. doi: 10.1073/pnas.1712538115. Epub 2018 Feb 7.
Neuromodulation of neural networks, whereby a selected circuit is regulated by a particular modulator, plays a critical role in learning and memory. Among neuromodulators, acetylcholine (ACh) plays a critical role in hippocampus-dependent memory and has been shown to modulate neuronal circuits in the hippocampus. However, it has remained unknown how ACh modulates hippocampal output. Here, using in vitro and in vivo approaches, we show that ACh, by activating oriens lacunosum moleculare (OLM) interneurons and therefore augmenting the negative-feedback regulation to the CA1 pyramidal neurons, suppresses the circuit from the hippocampal area CA1 to the deep-layer entorhinal cortex (EC). We also demonstrate, using mouse behavior studies, that the ablation of OLM interneurons specifically impairs hippocampus-dependent but not hippocampus-independent learning. These data suggest that ACh plays an important role in regulating hippocampal output to the EC by activating OLM interneurons, which is critical for the formation of hippocampus-dependent memory.
神经网络的神经调节，即通过特定的调制器调节选定的电路，在学习和记忆中起着关键作用。在神经调质中，乙酰胆碱（ACh）在海马体依赖的记忆中起着关键作用，并已被证明可以调节海马体中的神经元回路。然而，ACh 如何调节海马体输出仍然未知。在这里，我们使用体外和体内方法表明，ACh 通过激活或iens lacunosum moleculare（OLM）中间神经元并因此增强对 CA1 锥体神经元的负反馈调节，从而抑制从海马体 CA1 区到深层内嗅皮层（EC）的回路。我们还通过小鼠行为研究表明，OLM 中间神经元的消融特异性地损害了海马体依赖的但不是海马体独立的学习。这些数据表明，ACh 通过激活 OLM 中间神经元在调节海马体到 EC 的输出中起着重要作用，这对于海马体依赖记忆的形成至关重要。
