Synaptic Action in the Visual Cortex

描述（由申请人提供）：所有视觉信息都是通过基因皮质（GC）突触传递到皮层的，然而GC输入如何驱动皮层内的相互作用却知之甚少。常见的观点是，视觉激活，开始于视网膜，通过外侧膝状核（LGN）传递到第4层（L4）神经元。然后活动从L4层到2/3层（L2/3），然后是第5层（L5），然后是第6层（L6）。然而，有几条证据表明，这种描述过于简单化了。首先，虽然解剖学研究表明GC轴突主要支配L4和下L3，但额外的GC终端作用于L6和L1。虽然L6和L1的神经支配在解剖学上相对适度，但这些突触输入的功能影响可能是显著的。丘脑输入将平行驱动这些不同的层，其影响将取决于丘脑受体细胞之间的皮质内相互作用。第二，GC突触的突触强度和动态可能在形成视觉信息向皮层的传递中起重要作用。神经皮质突触是否特别有效和可靠是有争议的。不同类别的膝状接力神经元可能表现出不同的突触特性，但这尚未被探索。此外，GC输入针对不同类型的兴奋性和抑制性神经元，皮层突触后靶点的身份也可能影响GC突触的功能特性。GC突触突触特性的多样性可以改变正在进行的GC活动中兴奋和抑制的平衡，深刻影响皮层对视觉信息的加工。为了解决这些问题，我们将在GC神经元中选择性地表达一个光门控阳离子通道，通道视紫红质-2 (ChR2)，以孤立地光刺激GC纤维。结合我们在视觉皮层中不同类型的抑制性和兴奋性神经元的目标记录方面的丰富经验，这种新颖的方法将使我们能够全面了解在持续的视觉刺激过程中不同的GC输入如何驱动皮层回路。公共卫生相关性：拟议的实验将揭示视觉信息通过大脑流动的机制。了解这些机制将进一步加深我们对正常脑功能的理解，并促进神经和精神疾病的诊断和治疗。

Description (provided by applicant): All visual information is conveyed to the cortex via geniculocortical (GC) synapses, yet how GC inputs drive intracortical interactions is only poorly understood. The common view is that visual activation, initiated in the retina, is relayed through the lateral geniculate nucleus (LGN) to layer 4 (L4) neurons. Activity then flows through the cortex from L4 to layer 2/3 (L2/3), then layer 5 (L5) followed by layer 6 (L6). However, several lines of evidence suggest that this description is grossly simplified. First, while anatomical studies show that GC axons primarily innervate L4 and lower L3, additional GC terminals target L6 and L1. Although the innervation of L6 and L1 is relatively modest anatomically, the functional impact of these synaptic inputs may be significant. Thalamic input will drive these different layers in parallel, and its impact will depend on intracortical interactions among the thalamorecipient cells. Second, the synaptic strength and dynamics of GC synapses may play an important role in shaping the transmission of visual information to the cortex. Whether geniculocortical synapses are exceptionally efficacious and reliable is controversial. Different classes of geniculate relay neurons may exhibit distinct synaptic properties, but this has not been explored. Furthermore, GC inputs target different classes of excitatory and inhibitory neurons, and the identity of the cortical postsynaptic targets may also influence the functional properties of GC synapses. Diversity in the synaptic properties of GC synapses could change the balance of excitation and inhibition during ongoing GC activity, profoundly affecting cortical processing of visual information. To address these issues, we will selectively express a light-gated cation channel, channelrhodopsin-2 (ChR2), in GC neurons to optically stimulate GC fibers in isolation. Combined with our extensive experience in targeted recording from different classes of inhibitory and excitatory neurons in visual cortex, this novel approach will allow us to develop a comprehensive view of how different GC inputs drive cortical circuits during ongoing visual stimulation. PUBLIC HEALTH RELEVANCE: The proposed experiments will uncover mechanisms that underlie the flow of visual information through the brain. Understanding these mechanisms will further our understanding of normal brain function and facilitate the diagnosis and treatment of neurological and psychiatric disorders.