Chen Naiyan, Sugihara Hiroki, Sur Mriganka
Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Nat Neurosci. 2015 Jun;18(6):892-902. doi: 10.1038/nn.4002. Epub 2015 Apr 27.
Cholinergic modulation of cortex powerfully influences information processing and brain states, causing robust desynchronization of local field potentials and strong decorrelation of responses between neurons. We found that intracortical cholinergic inputs to mouse visual cortex specifically and differentially drive a defined cortical microcircuit: they facilitate somatostatin-expressing (SOM) inhibitory neurons that in turn inhibit parvalbumin-expressing inhibitory neurons and pyramidal neurons. Selective optogenetic inhibition of SOM responses blocked desynchronization and decorrelation, demonstrating that direct cholinergic activation of SOM neurons is necessary for this phenomenon. Optogenetic inhibition of vasoactive intestinal peptide-expressing neurons did not block desynchronization, despite these neurons being activated at high levels of cholinergic drive. Direct optogenetic SOM activation, independent of cholinergic modulation, was sufficient to induce desynchronization. Together, these findings demonstrate a mechanistic basis for temporal structure in cortical populations and the crucial role of neuromodulatory drive in specific inhibitory-excitatory circuits in actively shaping the dynamics of neuronal activity.
皮质的胆碱能调制对信息处理和脑状态有强大影响，会导致局部场电位强烈去同步化以及神经元之间反应的强去相关性。我们发现，小鼠视觉皮质的皮质内胆碱能输入特异性且差异性地驱动特定的皮质微回路：它们促进表达生长抑素（SOM）的抑制性神经元，而这些神经元反过来又抑制表达小白蛋白的抑制性神经元和锥体神经元。对SOM反应的选择性光遗传学抑制阻断了去同步化和去相关性，表明SOM神经元的直接胆碱能激活是这一现象所必需的。尽管在高胆碱能驱动水平下血管活性肠肽表达神经元被激活，但对其进行光遗传学抑制并未阻断去同步化。独立于胆碱能调制的直接光遗传学SOM激活足以诱导去同步化。这些发现共同证明了皮质群体中时间结构的机制基础，以及神经调节驱动在特定抑制性 - 兴奋性回路中积极塑造神经元活动动态方面的关键作用。
