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征的基本基础是LGN输入的时空模式以及第4层内细胞和电路的反应。LGN对皮层的输入依赖于时变的兴奋和抑制模式，以及这些过程与中继细胞（特别是t型钙通道）固有特性的相互作用。我们的初步证据表明，这些相互作用比我们之前认为的要复杂得多。这是因为(a)在LGN内至少有三种可证明的抑制类型；(b) t电流在塑造中继细胞输出中起连续渐变的作用，而不是像之前建议的那样在开或关模式下工作。此外，我们已经证明了LGN细胞爆发在驱动第4层细胞的膜电位（Vm）走向阈值方面的明显优势，而不是对孤立峰的影响。我们将测试三个特定的假设。在目标1中，我们将检验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假设，并且这些抑制过程对中继细胞的接受野的建立和它们的spike序列的及时形成至关重要。在Aim 2中，我们将验证以下假设：T电流对LGN细胞尖峰输出的贡献是时间和Vm的连续梯度函数，而不是以非此即彼的方式（爆发-张力）运作；此外，Aim 1中研究的不同类型的抑制将涉及不同数量的T电流。在目标3中，我们将测试关于LGN传入到初级视觉皮层第4层简单细胞的功能收敛的假设。具体来说，我们将验证单个第4层简单细胞从大量膝状传入事件接收兴奋性输入的假设，而不是细胞外研究提出的10到20个传入事件。我们还将验证一个假设，即单个LGN传入到给定的第4层简单细胞的低阈值爆发在形成皮层细胞反应中起决定性作用，包括它们的spike序列的精度和信息含量。我们将使用LGN和皮质层4的细胞内记录和LGN使用多个四极的细胞外记录的组合。