Synaptic organization of simple cell receptive fields

描述（由申请人提供）：初级视觉皮层中图像表征的基本基底是LGN输入的时空模式以及第4层内细胞和回路的响应。LGN输入到皮层是依赖于随时间变化的模式的兴奋和抑制，这些过程与中继细胞，特别是T-型钙通道的内在特性的相互作用。我们的初步证据表明，这些相互作用比以前想象的要复杂得多。这是因为（a）在LGN内至少有三种可证实的抑制类型，以及（B）T电流在中继细胞输出的成形中起着连续分级的作用，而不是如先前所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）朝向阈值方面的明显优势，与对孤立尖峰的影响相比。我们将测试三个具体的假设。在目标1中，我们将检验这样的假设：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和它们的形成至关重要。尖峰序列的时间。在目标2中，我们将检验T电流对LGN细胞锋电位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（爆发性）操作的假设，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，我们将测试关于LGN传入到初级视皮层第4层简单细胞的功能会聚的假设。具体来说，我们将测试的假设，个别层4简单的细胞接受兴奋性输入大量的膝状体传入，而不是10至20建议的细胞外研究。我们还将测试的假设，即在一个给定的第4层简单的细胞在形成皮层细胞的反应，包括精度和信息内容的尖峰列车的低阈值爆发在个别LGN传入发挥决定性作用。我们将使用LGN和皮质层4的细胞内记录和使用多个四极的LGN的细胞外记录的组合。 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多种类型脑疾病的临床方法的重要第一步，包括兴奋性改变，如癫痫或认知障碍，如精神分裂症。这些研究代表了第一个系统的方法来理解细胞和电路功能的视觉输入到皮层的丘脑中继，并在其对大脑皮层的输入层的影响。

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.