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胆碱能基底前脑为听觉皮层提供了一种与状态相关的感觉信号的并行通道。

The cholinergic basal forebrain provides a parallel channel for state-dependent sensory signaling to auditory cortex.

机构信息

Department of Psychological and Brain Sciences, Johns Hopkins University, Baltimore, MD, USA.

Department of Neuroscience, Johns Hopkins Medical Institute, Baltimore, MD, USA.

出版信息

Nat Neurosci. 2023 May;26(5):810-819. doi: 10.1038/s41593-023-01289-5. Epub 2023 Mar 27.

Abstract

Cholinergic basal forebrain (CBF) signaling exhibits multiple timescales of activity with classic slow signals related to brain and behavioral states and fast, phasic signals reflecting behavioral events, including movement, reinforcement and sensory-evoked responses. However, it remains unknown whether sensory cholinergic signals target the sensory cortex and how they relate to local functional topography. Here we used simultaneous two-channel, two-photon imaging of CBF axons and auditory cortical neurons to reveal that CBF axons send a robust, nonhabituating and stimulus-specific sensory signal to the auditory cortex. Individual axon segments exhibited heterogeneous but stable tuning to auditory stimuli allowing stimulus identity to be decoded from population activity. However, CBF axons displayed no tonotopy and their frequency tuning was uncoupled from that of nearby cortical neurons. Chemogenetic suppression revealed the auditory thalamus as a major source of auditory information to the CBF. Finally, slow fluctuations in cholinergic activity modulated the fast, sensory-evoked signals in the same axons, suggesting that a multiplexed combination of fast and slow signals is projected from the CBF to the auditory cortex. Taken together, our work demonstrates a noncanonical function of the CBF as a parallel channel for state-dependent sensory signaling to the sensory cortex that provides repeated representations of a broad range of sound stimuli at all points on the tonotopic map.

摘要

胆碱能基底前脑 (CBF) 信号表现出多种时间尺度的活动,经典的慢信号与大脑和行为状态有关,而快速、相位信号则反映行为事件,包括运动、强化和感觉诱发反应。然而,目前尚不清楚感觉胆碱能信号是否靶向感觉皮层,以及它们如何与局部功能拓扑相关。在这里,我们使用同时双通道、双光子成像技术对 CBF 轴突和听觉皮层神经元进行成像,揭示了 CBF 轴突向听觉皮层发送了一个强大的、非习惯化的、刺激特异性的感觉信号。单个轴突段对听觉刺激表现出不均匀但稳定的调谐,允许从群体活动中解码刺激身份。然而,CBF 轴突没有音调图,它们的频率调谐与附近皮质神经元的频率调谐无关。化学遗传抑制揭示了听觉丘脑是 CBF 向听觉信息的主要来源。最后,胆碱能活动的缓慢波动调节了同一轴突中的快速、感觉诱发信号,表明 CBF 向听觉皮层投射的是快速和慢速信号的混合组合。总之,我们的工作表明 CBF 具有非典型功能,可作为状态依赖的感觉信号向感觉皮层的并行通道,在音调图的所有点上提供广泛声音刺激的重复表示。

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