Department of Neurobiology and Anatomy, Brain Institute, University of Utah, Salt Lake City, Utah 84103, and Department of Anatomy and Neurobiology, Program in Neuroscience, University of Maryland School of Medicine, Baltimore, Maryland 21201.
J Neurosci. 2014 Mar 26;34(13):4654-64. doi: 10.1523/JNEUROSCI.5026-13.2014.
Cholinergic modulation of central circuits is associated with active sensation, attention, and learning, yet the neural circuits and temporal dynamics underlying cholinergic effects on sensory processing remain unclear. Understanding the effects of cholinergic modulation on particular circuits is complicated by the widespread projections of cholinergic neurons to telencephalic structures that themselves are highly interconnected. Here we examined how cholinergic projections from basal forebrain to the olfactory bulb (OB) modulate output from the first stage of sensory processing in the mouse olfactory system. By optogenetically activating their axons directly in the OB, we found that cholinergic projections from basal forebrain regulate OB output by increasing the spike output of presumptive mitral/tufted cells. Cholinergic stimulation increased mitral/tufted cell spiking in the absence of inhalation-driven sensory input and further increased spiking responses to inhalation of odorless air and to odorants. This modulation was rapid and transient, was dependent on local cholinergic signaling in the OB, and differed from modulation by optogenetic activation of cholinergic neurons in basal forebrain, which led to a mixture of mitral/tufted cell excitation and suppression. Finally, bulbar cholinergic enhancement of mitral/tufted cell odorant responses was robust and occurred independent of the strength or even polarity of the odorant-evoked response, indicating that cholinergic modulation adds an excitatory bias to mitral/tufted cells as opposed to increasing response gain or sharpening response spectra. These results are consistent with a role for the basal forebrain cholinergic system in dynamically regulating the sensitivity to or salience of odors during active sensing of the olfactory environment.
胆碱能调制的中枢回路与主动感觉、注意力和学习有关,但胆碱能对感觉处理的影响所涉及的神经回路和时间动态仍不清楚。理解胆碱能调制对特定回路的影响很复杂,因为胆碱能神经元广泛投射到端脑结构,而这些结构本身高度互联。在这里,我们研究了基底前脑到嗅球(OB)的胆碱能投射如何调节小鼠嗅觉系统中第一级感觉处理的输出。通过光遗传学直接在 OB 中激活它们的轴突,我们发现基底前脑的胆碱能投射通过增加假定的僧帽细胞/丛细胞的尖峰输出来调节 OB 的输出。胆碱能刺激增加了僧帽细胞/丛细胞在没有吸入驱动的感觉输入的情况下的尖峰活动,并进一步增加了对无味空气和气味剂的尖峰反应。这种调制是快速和短暂的,依赖于 OB 中的局部胆碱能信号,并且与基底前脑中通过光遗传学激活胆碱能神经元的调制不同,后者导致僧帽细胞/丛细胞兴奋和抑制的混合。最后,OB 胆碱能增强僧帽细胞/丛细胞对气味剂的反应是强大的,并且独立于气味剂诱发反应的强度甚至极性发生,表明胆碱能调制相对于增加反应增益或锐化反应谱,向僧帽细胞/丛细胞添加兴奋性偏向。这些结果与基底前脑胆碱能系统在主动感知嗅觉环境期间动态调节对气味的敏感性或显著性的作用一致。