Brainstem Control of Subcortical Visual Information

描述（由申请人提供）：背外侧膝状体核 (LGN)是感知链中至关重要的一环视网膜神经节细胞编码 并将其传输到LGN。大多数人认为， 信息发生在retinogeniculate突触，但一个完整的机制， 难以捉摸。我们最近的研究结果表明，一些新的和令人兴奋的来源， 在LGN上动态控制视觉信息。其中两个是已知的 中继神经元的调节剂：胆碱能臂旁脑干（PBR）和 大量的皮质膝状体反馈。PBR释放一氧化氮 (NO)我们的数据表明NO影响视网膜的方式存在惊人的差异， 和皮层输入。NO具有强大的和选择性的抑制作用， 通过与NMDA的相互作用在LGN中进行视网膜膝状体传递 受体;然而，通过CG途径的传输被两个 不同的机制。丘脑功能的另一个未解之谜是 皮质反馈的目的是从第6层LGN，我们现在看到的是 与PBR和NO密切相关。我们提出了一系列新的实验 揭示PBR的贡献，以及皮质反馈的影响， 一个全球性的假设，即视觉需要双方的合作活动模式， 这些途径。目的1：NO如何影响LGN中继细胞膜 财产？NO抑制视网膜神经节NMDA受体功能 通路我们假设NO也靶向低阈值钙电流 （I（T））和关键K+电流（I）（As））。我将以我的智慧和智慧， 来自LGN切片的细胞内斑片记录，同时递送NO 供体和清道夫，并通过刺激内在的NO生产，通过 bNOS酶目的2：NO如何影响LGN中继细胞的快速突触输入？ 我们将刺激视网膜和CG通路（以唤起GABA能IPSP/JPSC） 和CG通路（以诱发脑电能EPSP/EPSC）， 操纵NO水平。我们假设一氧化氮如何影响 视网膜和皮层EPSP/EPSC;皮层EPSP/EPSC增强，表明 PBR，通过NO，可以将平衡从视网膜前馈转移， 处理和皮层反馈处理。目标3：如何 皮质膝状体投射控制丘脑皮质对话？中继小区 以两种模式之一对视网膜输入作出反应，突发或紧张。我们假设 该层6促进爆发和紧张性反应的视敏梯度，以及 同步点火，在LGN。我们将从丘脑合奏中记录， 视觉处理，在激活和失活视觉皮层的第6层时， 同时激活脑干通路。视网膜输入对LGN的影响是 众所周知，但该领域正在努力解决 视网膜外突触的影响这些问题的答案将 彻底改变了我们对丘脑功能的看法， 周边与皮层的合作伙伴在一起捆绑视觉线程 perception.

DESCRIPTION (provided by applicant): The dorsal lateral geniculate nucleus (LGN) is a vital link in the chain of perception. Retinal ganglion cells encode the visual world and transmit it to the LGN. Most agree that gating of this information occurs at the retinogeniculate synapse, but a complete mechanism is elusive. Our recent findings demonstrate several new and exciting sources of dynamic control of visual information at the LGN. Two of these are known modulators of relay neurons: the cholinergic parabrachial brainstem (PBR) and the massive corticogeniculate (CG) feedback. The PBR releases nitric oxide (NO), and our data indicate an amazing difference in the way NO affects retinal and cortical inputs. NO has a powerful and selective inhibitory influence on retinogeniculate transmission in the LGN through interaction with the NMDA receptor; however, transmission through the CG pathway is enhanced by two separate mechanisms. The other great remaining mystery of thalamic function is the purpose of the cortical feedback to LGN from layer 6, which we now see as intimately linked with the PBR and NO. We propose a new series of experiments to reveal the contributions of the PBR, and cortical feedback influences, with a global hypothesis that vision requires cooperative activity patterns of both of these pathways. Aim 1: How does NO affect LGN relay cell membrane properties? NO suppresses NMDA receptor function in the retinogeniculate pathway. We hypothesize that NO also targets the low threshold Ca2+ current (I(T)) and a key K+ currents (I) (As)). We will probe I(T) and I(As) with intracellular patch recordings from slices of the LGN, while delivering NO donors and scavengers, and by stimulating intrinsic NO production through the enzyme bNOS. Aim 2: How does NO affect fast synaptic inputs to LGN relay cells? We will stimulate the retinal and CG pathways (to evoke GABAergic IPSP/JPSCs) and the CG pathway (to evoke glutamatergic EPSP/EPSCs) in slices while manipulating NO levels. We hypothesize a stark difference in how NO affects retinal and cortical EPSP/EPSCs; cortical EPSP/EPSCs are enhanced, indicating that the PBR, through NO, may shift the balance away from retinal feedforward processing and toward cortical feedback processing. Aim 3: How does the corticogeniculate projection control the thalamocortical dialog? Relay cells respond to retinal inputs in one of two modes, burst or tonic. We hypothesize that layer 6 promotes a visuotopic gradient of burst and tonic responses, and synchronous firing, in the LGN. We will record from thalamic ensembles during visual processing, while activating and inactivating layer 6 of visual cortex, and while activating brainstem pathways. The impact of retinal inputs to LGN is well known, but the field is struggling with the nature and scope of extraretinal synaptic influences. The answers to these questions will completely transform our view of thalamic function from that of a slave of the periphery to a partner with cortex in binding together the threads of visual perception.