Synaptic organization of simple cell receptive fields

描述(申请人提供)：初级视觉皮质的图像表征的基本底物是LGN输入的时空模式以及第四层内细胞和回路的反应。LGN输入到皮层依赖于兴奋和抑制的时变模式，以及这些过程与中继细胞的固有特性，特别是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，以及(B)T-电流在塑造中继单元输出方面扮演着持续递增的角色，而不是像先前所建议的那样以开或关模式工作。此外，我们还证明了与孤立的棘波相比，LGN细胞爆发在驱动第4层细胞的膜电位(Vm)接近阈值方面具有明显的优势。我们将测试三个具体的假设。在目标1中，我们将检验这样一个假设，即LGN神经元对视觉刺激的反应至少由三种不同的抑制形式形成，这些抑制过程对于建立中继细胞的感受野和及时形成它们的棘波序列至关重要。在目标2中，我们将检验这样的假设，即T电流对LGN细胞棘波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运行(爆发性强直)，此外，目标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，我们将检验有关LGN传入细胞与初级视皮层第四层简单细胞的功能会聚的假说。具体地说，我们将测试这样一种假设，即单个第四层简单细胞从大量膝状传入细胞接受兴奋性输入，而不是细胞外研究建议的10到20个。我们还将检验这一假设，即特定第四层简单细胞的单个LGN传入的低阈值爆发在塑造皮层细胞反应包括其棘波序列的精确度和信息含量方面起决定性作用。我们将使用来自LGN和皮质第四层的细胞内记录和来自LGN的使用多个四极管的细胞外记录的组合。

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.