Sottile Sarah Y, Hackett Troy A, Cai Rui, Ling Lynne, Llano Daniel A, Caspary Donald M
Department of Pharmacology and.
Department of Hearing and Speech Sciences, Vanderbilt University Medical Center, Nashville, Tennessee 37232, and.
J Neurosci. 2017 Nov 22;37(47):11377-11389. doi: 10.1523/JNEUROSCI.1795-17.2017. Epub 2017 Oct 23.
Acetylcholine (ACh) is a potent neuromodulator capable of modifying patterns of acoustic information flow. In auditory cortex, cholinergic systems have been shown to increase salience/gain while suppressing extraneous information. However, the mechanism by which cholinergic circuits shape signal processing in the auditory thalamus (medial geniculate body, MGB) is poorly understood. The present study, in male Fischer Brown Norway rats, seeks to determine the location and function of presynaptic neuronal nicotinic ACh receptors (nAChRs) at the major inputs to MGB and characterize how nAChRs change during aging. electrophysiological/optogenetic methods were used to examine responses of MGB neurons after activation of nAChRs during a paired-pulse paradigm. Presynaptic nAChR activation increased responses evoked by stimulation of excitatory corticothalamic and inhibitory tectothalamic terminals. Conversely, nAChR activation appeared to have little effect on evoked responses from inhibitory thalamic reticular nucleus and excitatory tectothalamic terminals. hybridization data showed nAChR subunit transcripts in GABAergic inferior colliculus neurons and glutamatergic auditory cortical neurons supporting the present slice findings. Responses to nAChR activation at excitatory corticothalamic and inhibitory tectothalamic inputs were diminished by aging. These findings suggest that cholinergic input to the MGB increases the strength of tectothalamic inhibitory projections, potentially improving the signal-to-noise ratio and signal detection while increasing corticothalamic gain, which may facilitate top-down identification of stimulus identity. These mechanisms appear to be affected negatively by aging, potentially diminishing speech perception in noisy environments. Cholinergic inputs to the MGB appear to maximize sensory processing by adjusting both top-down and bottom-up mechanisms in conditions of attention and arousal. The pedunculopontine tegmental nucleus is the source of cholinergic innervation for sensory thalamus and is a critical part of an ascending arousal system that controls the firing mode of thalamic cells based on attentional demand. The present study describes the location and impact of aging on presynaptic neuronal nicotinic acetylcholine receptors (nAChRs) within the circuitry of the auditory thalamus (medial geniculate body, MGB). We show that nAChRs are located on ascending inhibitory and descending excitatory presynaptic inputs onto MGB neurons, likely increasing gain selectively and improving temporal clarity. In addition, we show that aging has a deleterious effect on nAChR efficacy. Cholinergic dysfunction at the level of MGB may affect speech understanding negatively in the elderly population.
乙酰胆碱（ACh）是一种强效神经调节剂，能够改变听觉信息流的模式。在听觉皮层中，胆碱能系统已被证明可增加显著性/增益，同时抑制无关信息。然而，胆碱能回路在听觉丘脑（内侧膝状体，MGB）中塑造信号处理的机制却知之甚少。本研究以雄性Fischer Brown Norway大鼠为对象，旨在确定MGB主要输入处突触前神经元烟碱型乙酰胆碱受体（nAChRs）的位置和功能，并描述nAChRs在衰老过程中的变化。采用电生理/光遗传学方法，在配对脉冲范式中激活nAChRs后，检测MGB神经元的反应。突触前nAChR激活增强了兴奋性皮质丘脑和抑制性顶盖丘脑终末刺激所诱发的反应。相反，nAChR激活似乎对抑制性丘脑网状核和兴奋性顶盖丘脑终末诱发的反应影响不大。杂交数据显示，GABA能下丘神经元和谷氨酸能听觉皮层神经元中有nAChR亚基转录本，支持当前切片研究结果。随着衰老，兴奋性皮质丘脑和抑制性顶盖丘脑输入对nAChR激活的反应减弱。这些发现表明，MGB的胆碱能输入增强了顶盖丘脑抑制性投射的强度，可能提高信噪比和信号检测能力，同时增加皮质丘脑增益，这可能有助于自上而下识别刺激特征。这些机制似乎受到衰老的负面影响，可能会降低老年人在嘈杂环境中的言语感知能力。MGB的胆碱能输入似乎通过在注意力和觉醒状态下调节自上而下和自下而上的机制，使感觉处理达到最大化。脚桥被盖核是感觉丘脑胆碱能神经支配的来源，是基于注意力需求控制丘脑细胞放电模式的上行觉醒系统的关键部分。本研究描述了衰老对听觉丘脑（内侧膝状体，MGB）回路中突触前神经元烟碱型乙酰胆碱受体（nAChRs）的位置和影响。我们表明，nAChRs位于MGB神经元的上行抑制性和下行兴奋性突触前输入上，可能选择性地增加增益并提高时间清晰度。此外，我们表明衰老对nAChR效能有有害影响。MGB水平的胆碱能功能障碍可能对老年人群的言语理解产生负面影响。
