Mechanisms of Synaptic Processing in the Retina

描述(申请人提供)：大脑如何根据光线通过视网膜的模式来决定外部运动的方向，几十年来一直困扰着神经科学家。编码图像运动方向的神经元首先出现在视网膜上。神经元是开关方向选择性神经节细胞(DSGCs)。我们将单独研究产生方向选择性的会聚突触机制，并确定它们是如何产生的，以及它们是如何被DSGC整合的。将该系统获得的结果与其他大脑区域和其他物种的结果进行比较，将为神经电路如何移除冗余信息，并从传入的突触活动中提取特定特征或模式提供新的见解。 每个DSGC确定图像在一小块视觉空间中运动的方向。这些细胞最有选择性地沿着首选零轴移动。它们的响应在首选方向上移动时最大，而在相反的零方向上移动时最小。我们的初步记录表明，多种突触机制的混合会产生方向选择性反应。DSGCs的兴奋性和抑制性输入是定向的，表明中间神经元的神经递质释放存在突触前调制。定向反应也产生于双侧丘脑皮质的树突内，并产生于兴奋性和抑制性突触输入的突触后整合。一个惊人的发现是，DSGCs的两个不同的树突分枝使用不同的突触机制来产生定向信号。 这项拟议的研究将使用全细胞膜片钳记录技术来分析DSGCs在体外兔视网膜标本中视觉诱发的突触反应。第一个目标将确定侧向抑制的起源和性质，侧向抑制对产生方向选择反应至关重要。第二个目标是确定向DSGCs产生定向兴奋性输入的突触机制。第三个目标将进一步检验这两个树突层使用不同的突触机制产生定向信号的假设。

DESCRIPTION (provided by applicant): How the brain resolves the direction of external motion from the pattern of light passing across the retina has puzzled neuroscientists for decades. Neurons that encode the direction of image motion are first encountered in the retina. The neurons are the on-off direction-selective ganglion cells (DSGCs). We will examine in isolation the convergent synaptic mechanisms that generate direction selectivity, and determine how they arise, and how they are integrated by the DSGC. Comparison of the results obtained from this system, with those in other brain regions and other species, will provide new insights into how neural circuits remove redundant information, and extract specific features or patterns from the barrage of incoming synaptic activity. Each DSGC determines the direction of image motion in a small region of visual space. These cells are most selective for movement along a preferred-null axis. Their responses are largest for movement in the preferred direction and smallest for movement in the opposite, null direction. Our preliminary recordings indicate that a mix of synaptic mechanisms generate direction-selective responses. The excitatory and inhibitory inputs to DSGCs are directional, indicating that there is presynaptic modulation of neurotransmitter release from interneurons. Directional responses are also generated within the dendrites of the DSGC, and arise from the postsynaptic integration of excitatory and inhibitory synaptic inputs. A striking finding is that the two distinct dendritic arbors of DSGCs use different synaptic mechanisms to generate a directional signal. The proposed research will use whole-cell patch-clamp recording techniques to analyse the visually evoked synaptic responses in DSGCs in an in vitro rabbit retina preparation. The first aim will determine the origin and nature of the lateral inhibition that is critical for generating direction-selective responses. The second aim will be to determine the synaptic mechanisms that generate directional excitatory inputs to the DSGCs. The third aim will further test the hypothesis that the two dendritic strata generate directional signals using different synaptic mechanisms.