Department of Anatomy & Neurobiology, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA.
Curr Biol. 2013 Sep 23;23(18):1746-55. doi: 10.1016/j.cub.2013.07.033. Epub 2013 Aug 29.
Cortical inhibition plays a critical role in controlling and modulating cortical excitation, and a more detailed understanding of the neuronal circuits contributing to each will provide more insight into their roles in complex cortical computations. Traditional neuronal tracers lack a means for easily distinguishing between circuits of inhibitory and excitatory neurons. To overcome this limitation, we have developed a technique for retrogradely labeling inputs to local clusters of inhibitory or excitatory neurons, but not both, using neurotropic adenoassociated and lentiviral vectors, cell-type-specific promoters, and a modified rabies virus.
Applied to primary visual cortex (V1) in mouse, the cell-type-specific tracing technique labeled thousands of presynaptically connected neurons and revealed that the dominant source of input to inhibitory and excitatory neurons is local in origin. Neurons in other visual areas are also labeled; the percentage of these intercortical inputs to excitatory neurons is somewhat higher (~20%) than to inhibitory neurons (<10%), suggesting that intercortical connections have less direct control over inhibition. The inputs to inhibitory neurons were also traced in cat V1, and when aligned with the orientation preference map revealed for the first time that long-range inputs to inhibitory neurons are well tuned to orientation.
These novel findings for inhibitory and excitatory circuits in the visual cortex demonstrate the efficacy of our new technique and its ability to work across species, including larger-brained mammals such as the cat. This paves the way for a better understanding of the roles of specific cell types in higher-order perceptual and cognitive processes.
皮层抑制在控制和调节皮层兴奋方面起着关键作用，对促成每个抑制和兴奋神经元回路的更详细理解将有助于深入了解它们在复杂皮层计算中的作用。传统的神经元示踪剂缺乏一种简单区分抑制性和兴奋性神经元回路的方法。为了克服这一限制，我们开发了一种使用神经亲和性腺相关病毒和慢病毒载体、细胞类型特异性启动子以及改良的狂犬病毒，来逆行标记局部抑制性或兴奋性神经元簇输入而不是两者的技术。
该技术应用于小鼠初级视觉皮层（V1），细胞类型特异性示踪技术标记了数千个突触前连接神经元，并揭示了抑制性和兴奋性神经元的主要输入源来源于局部。其他视觉区域的神经元也被标记；这些皮质间输入到兴奋性神经元的比例（约 20%）略高于到抑制性神经元（<10%），这表明皮质间连接对抑制的控制作用较小。在猫的 V1 中也追踪了抑制性神经元的输入，并且当与首次揭示的朝向偏好图对齐时，发现长程输入到抑制性神经元的朝向调谐良好。
这些关于视觉皮层中抑制性和兴奋性回路的新发现证明了我们新技术的有效性及其在跨物种中的应用能力，包括猫等大脑较大的哺乳动物。这为更好地了解特定细胞类型在更高阶感知和认知过程中的作用铺平了道路。
