Synaptic Action in the Visual Cortex

描述（由申请人提供）：所有视觉信息都通过膝状皮质（GC）突触传递到皮质，但GC输入如何驱动皮质内相互作用仍知之甚少。通常的观点是，视觉激活，在视网膜中启动，通过外侧膝状体核（LGN）传递到第4层（L4）神经元。然后，活动从L4流经皮层到第2/3层（L2/3），然后是第5层（L5），然后是第6层（L 6）。然而，一些证据表明，这一描述被大大简化了。首先，虽然解剖学研究表明GC轴突主要支配L4和L3下部，但其他GC终末靶向L 6和L1。虽然L 6和L1的神经支配在解剖学上相对温和，但这些突触输入的功能影响可能是显著的。丘脑输入将驱动这些不同的层并行，其影响将取决于丘脑感受器细胞之间的皮质内相互作用。第二，GC突触的突触强度和动力学可能在塑造视觉信息到皮层的传输中起重要作用。膝状皮质突触是否特别有效和可靠是有争议的。不同类别的膝状体中继神经元可能表现出不同的突触特性，但这还没有被探索。此外，GC输入针对不同类别的兴奋性和抑制性神经元，并且皮层突触后靶点的身份也可能影响GC突触的功能特性。GC突触的突触特性的多样性可以改变GC活动过程中兴奋和抑制的平衡，深刻影响视觉信息的皮层处理。为了解决这些问题，我们将选择性地表达一个光门控阳离子通道，通道视紫红质-2（ChR 2），在GC神经元中光学刺激孤立的GC纤维。结合我们在视觉皮层中不同类别的抑制性和兴奋性神经元的靶向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不同的GC输入如何在持续的视觉刺激过程中驱动皮层回路。公共卫生相关性：拟议的实验将揭示视觉信息在大脑中流动的机制。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.