Division of Neurobiology, Department of Molecular Cell Biology, Helen Wills Neuroscience Institute, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Curr Biol. 2012 Aug 21;22(16):1459-67. doi: 10.1016/j.cub.2012.06.007. Epub 2012 Jun 28.
A fundamental process underlying all brain functions is the propagation of spiking activity in networks of excitatory and inhibitory neurons. In the neocortex, although functional connections between pairs of neurons have been studied extensively in brain slices, they remain poorly characterized in vivo, where the high background activity, global brain states, and neuromodulation can powerfully influence synaptic transmission. To understand how spikes are transmitted in cortical circuits in vivo, we used two-photon calcium imaging to monitor ensemble activity and targeted patching to stimulate a single neuron in mouse visual cortex.
Burst spiking of a single pyramidal neuron can drive spiking activity in both excitatory and inhibitory neurons within a ∼100 μm radius. For inhibitory neurons, ∼30% of the somatostatin interneurons fire reliably in response to a presynaptic burst of ≥5 spikes. In contrast, parvalbumin interneurons showed no detectable responses to single-neuron stimulation, but their spiking is highly correlated with the local network activity.
Our results demonstrate the feasibility of mapping functional connectivity at cellular resolution in vivo and reveal distinct operations of two major inhibitory circuits, one detecting single-neuron spike bursts and the other reflecting distributed network activity.
所有大脑功能的基础过程是兴奋和抑制神经元网络中尖峰活动的传播。在大脑皮层中，尽管已经在脑片上广泛研究了神经元之间的功能连接，但它们在体内的特征仍然很差，因为高背景活动、全局大脑状态和神经调制可以强烈影响突触传递。为了了解在体内皮质回路中尖峰是如何传递的，我们使用双光子钙成像来监测神经元群体活动，并靶向刺激小鼠视觉皮层中的单个神经元。
单个锥体神经元的爆发性尖峰可以驱动半径约为 100 μm 的兴奋和抑制神经元中的尖峰活动。对于抑制性神经元，在前突触爆发超过 5 个尖峰时，约 30%的生长抑素中间神经元可靠地放电。相比之下，脑啡肽能中间神经元对单个神经元的刺激没有可检测到的反应，但它们的放电与局部网络活动高度相关。
我们的结果证明了在体内以细胞分辨率绘制功能连接图的可行性，并揭示了两个主要抑制性回路的不同作用，一个回路检测单个神经元的尖峰爆发，另一个回路反映分布式网络活动。
