Optogenetic Activation of Basal Forebrain Cholinergic Neurons Modulates Neuronal Excitability and Sensory Responses in the Main Olfactory Bulb
Optogenetic Activation of Basal Forebrain Cholinergic Neurons Modulates Neuronal Excitability and Sensory Responses in the Main Olfactory Bulb
复制标题
DOI：
10.1523/jneurosci.0058-12.2012
复制
发表时间：
2012-07-25
影响因子：
5.3
通讯作者：
Luo, Minmin
中科院分区：
文献类型：
--
作者：
Ma, Ming;Luo, Minmin
哺乳动物的主嗅球（MOB）接受来自基底前脑Broca斜角带水平支（HDB）胆碱能神经元的大量离心输入，其活动被认为与动物的行为状态（如注意力）相关。球中的胆碱能信号促进嗅觉辨别和学习，但HDB胆碱能神经元的活性如何调节MOB中神经元的兴奋性和嗅觉反应仍然存在争议。在这项研究中，我们使用光遗传学的方法来选择性地激活HDB胆碱能神经元，并记录这种激活对小鼠MOB神经元自发放电活动和气味诱发反应的影响。对细胞进行单细胞标记，并从形态学上确定其特定类型。我们发现，光刺激HDB胆碱能神经元抑制所有主要细胞类型的自发放电活动，包括二尖瓣/簇状（M/T）细胞，肾小球周围（PG）细胞和GABA能颗粒细胞。在10 Hz的刺激下，抑制作用显著产生，并在更高的频率下进一步增强。此外，胆碱能激活锐化了大多数的M/T细胞的嗅觉调谐曲线，但广泛增强PG细胞和颗粒细胞的气味诱发反应。这些结果表明，基底前脑胆碱能系统对调制神经元兴奋性的MOB和支持的假设，胆碱能活性增加嗅觉辨别能力的强烈影响。
The main olfactory bulb (MOB) in mammals receives massive centrifugal input from cholinergic neurons in the horizontal limb of the diagonal band of Broca (HDB) in the basal forebrain, the activity of which is thought to be correlated with animal behaving states, such as attention. Cholinergic signals in the bulb facilitate olfactory discrimination and learning, but it has remained controversial how the activity of HDB cholinergic neurons modulates neuronal excitability and olfactory responses in the MOB. In this study, we used an optogenetic approach to selectively activate HDB cholinergic neurons and recorded the effect of this activation on the spontaneous firing activity and odor-evoked responses of mouse MOB neurons. Cells were juxtacellularly labeled and their specific types were morphologically determined. We find that light stimulation of HDB cholinergic neurons inhibits the spontaneous firing activity of all major cell types, including mitral/tufted (M/T) cells, periglomerular (PG) cells, and GABAergic granule cells. Inhibitions are significantly produced by stimulation at 10 Hz and further enhanced at higher frequencies. In addition, cholinergic activation sharpens the olfactory tuning curves of a majority of M/T cells but broadly potentiates odor-evoked responses of PG cells and granule cells. These results demonstrate strong effects of the basal forebrain cholinergic system on modulating neuronal excitability in the MOB and support the hypothesis that cholinergic activity increases olfactory discrimination capability.