Systemic Nicotine Increases Gain and Narrows Receptive Fields in A1 via Integrated Cortical and Subcortical Actions
Systemic Nicotine Increases Gain and Narrows Receptive Fields in A1 via Integrated Cortical and Subcortical Actions
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DOI：
10.1523/eneuro.0192-17.2017
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发表时间：
2017-05-01
期刊：
影响因子：
3.4
通讯作者：
Metherate, Raju
中科院分区：
文献类型：
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作者：
Askew, Caitlin;Intskirveli, Irakli;Metherate, Raju
尼古丁通过作用于烟碱乙酰胆碱受体（nAChR）来增强感觉和认知加工，但确切的回路和系统水平机制仍不清楚。在感觉皮层，烟碱调制的感受野（RFs）提供了一个模型，探测机制，nAChRs调节皮层电路。在这里，我们使用一种新颖的电生理方法来检查小鼠初级听觉皮质（A1）中的RF调制：对陷波噪声音调（TINN）声学刺激反应的电流源密度（CSD）分析。TINN刺激由嵌入在白色噪声刺激内的记录部位的特征频率（CF）处的音调组成，所述噪声刺激被过滤以创建以CF为中心的可变宽度的频谱“陷波”。全身尼古丁（2.1 mg/kg）增强了对CF音和窄切迹刺激的反应，但降低了对宽切迹刺激的反应，表明在窄RF内反应增益增加。随后的操作表明，调制皮质RF全身尼古丁反映了在听觉通路的几个层次的影响：尼古丁抑制听觉中脑和丘脑的反应，抑制与CF的光谱距离增加，使RF变得更窄，并促进丘脑皮质通路的反应，而A1内的尼古丁作用进一步促进抑制和促进。因此，全身性尼古丁的多种效应沿上行听觉通路整合沿着。这些行动在nAChRs在皮层和皮层下的电路，模仿听觉注意力的影响，可能有助于烟碱增强感觉和认知处理。
Nicotine enhances sensory and cognitive processing via actions at nicotinic acetylcholine receptors (nAChRs), yet the precise circuit-and systems-level mechanisms remain unclear. In sensory cortex, nicotinic modulation of receptive fields (RFs) provides a model to probe mechanisms by which nAChRs regulate cortical circuits. Here, we examine RF modulation in mouse primary auditory cortex (A1) using a novel electrophysiological approach: current-source density (CSD) analysis of responses to tone-in-notched-noise (TINN) acoustic stimuli. TINN stimuli consist of a tone at the characteristic frequency (CF) of the recording site embedded within a white noise stimulus filtered to create a spectral "notch" of variable width centered on CF. Systemic nicotine (2.1 mg/kg) enhanced responses to the CF tone and to narrow-notch stimuli, yet reduced the response to wider-notch stimuli, indicating increased response gain within a narrowed RF. Subsequent manipulations showed that modulation of cortical RFs by systemic nicotine reflected effects at several levels in the auditory pathway: nicotine suppressed responses in the auditory midbrain and thalamus, with suppression increasing with spectral distance from CF so that RFs became narrower, and facilitated responses in the thalamocortical pathway, while nicotinic actions within A1 further contributed to both suppression and facilitation. Thus, multiple effects of systemic nicotine integrate along the ascending auditory pathway. These actions at nAChRs in cortical and subcortical circuits, which mimic effects of auditory attention, likely contribute to nicotinic enhancement of sensory and cognitive processing.