Synaptic organization of simple cell receptive fields

简单细胞感受野的突触组织

• 批准号: 8549369
• 负责人: Diego Contreras
• 金额: $ 3.7万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8549369
• 关键词: Automobile Driving; Brain Diseases; Cells; Cerebral cortex; Clinical; Cognition Disorders; Complex; Epilepsy; Felis catus; Image; Individual; Injection of therapeutic agent; Membrane Potentials; Neurons; Output; Pattern; Photic Stimulation; Play; Process; Property; Public Health; Role; Schizophrenia; Shapes; Synapses; T-Type Calcium Channels; Testing; Thalamic structure; Time; Training; Visual; Work; area striata; channel blockers; extracellular; in vivo; public health relevance; receptive field; research study; response; spatiotemporal; visual control; visual stimulus

DESCRIPTION (provided by applicant): The essential substrate for image representation in primary visual cortex is the spatiotemporal pattern of LGN input and the responses of cells and circuits within layer 4. The LGN input to cortex is dependent on time-varying patterns of excitation and inhibition and on the interactions of these processes with the intrinsic properties of relay cells, especially T-type calcium channels. Our preliminary evidence shows that these interactions are far more complex than previously thought. This is so because (a) there are at least three demonstrable types of inhibition within the LGN and (b) T-currents play a continuously graded role in shaping relay cell output rather than working in an either on or off mode as previously suggested. Further, we have demonstrated the distinct advantage of LGN cell bursts in driving the membrane potential (Vm) of layer 4 cells towards threshold as compared to the effects on isolated spikes. We will test three specific hypotheses. In Aim 1, we will test the hypothesis that responses of LGN neurons to visual stimuli are shaped by at least three distinct forms of inhibition and that these inhibitory processes are critical to the establishment of the receptive fields of relay cells and to the shaping of their spike trains in time. In Aim 2, we will test the hypothesis that the contribution of T- currents to LGN cell spike output is a continuously graded function of time and Vm rather than operating in an either-or fashion (burst-tonic), and, furthermore, that different types of inhibition studied in Aim 1 will engage different amounts of T-current. In Aim 3, we will test hypotheses regarding the functional convergence of LGN afferents onto layer 4 simple cells in primary visual cortex. Specifically, we will test the hypothesis that individual layer 4 simple cells receive excitatory input from large numbers of geniculate afferents rather than to 10 to 20 suggested by extracellular studies. We will also test the hypothesis that low threshold bursts in individual LGN afferents to a given layer 4 simple cell play a decisive role in shaping cortical cell responses including the precision and information content of their spike trains. We will use a combination of intracellular recordings from LGN and cortical layer 4 and extracellular recordings from LGN using multiple tetrodes. PUBLIC HEALTH RELEVANCE: Understanding cortical function and the interaction of thalamus and cortex are an essential first step towards developing clinical approaches to multiple types of brain disorders including alterations in excitability such as epilepsy or cognitive disorders such as schizophrenia. These studies represent the first systematic approach to understanding cellular and circuit function in the thalamic relay of visual inputs to cortex and in their impact on the input layer of the cerebral cortex.

描述（由申请人提供）：初级视觉皮层中图像表示的基本基础是 LGN 输入的时空模式以及第 4 层内细胞和电路的响应。皮层的 LGN 输入取决于激励和时变模式。抑制以及这些过程与中继细胞固有特性（尤其是 T 型钙通道）的相互作用。我们的初步证据表明，这些相互作用比之前想象的要复杂得多。之所以如此，是因为 (a) LGN 内至少存在三种明显的抑制类型，(b) T 电流在塑造继电器单元输出方面发挥连续分级的作用，而不是像之前建议的那样工作在开或关模式下。此外，我们还证明了与对孤立尖峰的影响相比，LGN 细胞爆发在将第 4 层细胞的膜电位 (Vm) 推向阈值方面具有明显的优势。我们将测试三个具体假设。在目标 1 中，我们将检验这一假设，即 LGN 神经元对视觉刺激的反应是由至少三种不同形式的抑制形成的，并且这些抑制过程对于中继细胞感受野的建立及其神经元的形成至关重要。及时高峰列车。在目标 2 中，我们将测试以下假设：T 电流对 LGN 单元尖峰输出的贡献是时间和 Vm 的连续分级函数，而不是以非此即彼的方式（突发主调）运行，此外，目标 1 中研究的不同类型的抑制将涉及不同量的 T 电流。在目标 3 中，我们将测试有关 LGN 传入神经向初级视觉皮层第 4 层简单细胞功能收敛的假设。具体来说，我们将测试以下假设：单个第 4 层简单细胞接收来自大量膝状传入神经的兴奋性输入，而不是细胞外研究建议的 10 到 20 个。我们还将测试以下假设：单个 LGN 传入到给定第 4 层简单细胞的低阈值爆发在塑造皮质细胞反应（包括其尖峰序列的精度和信息内容）方面发挥决定性作用。我们将使用来自 LGN 和皮质层 4 的细胞内记录以及使用多个四极管的 LGN 细胞外记录的组合。 公共卫生相关性：了解皮质功能以及丘脑和皮质的相互作用是开发治疗多种类型脑部疾病（包括癫痫等兴奋性改变或精神分裂症等认知障碍）临床方法的重要第一步。这些研究代表了第一个系统方法来了解视觉输入到皮层的丘脑中继中的细胞和电路功能及其对大脑皮层输入层的影响。