Dynamic Properties of Visual Cortical Cirucits

描述（由申请人提供）：从视网膜到视觉皮层的主要途径是通过丘脑外侧膝状核。虽然视网膜输入驱动丘脑中继细胞放电并勾勒出它们的接受野，但丘脑中尚未确定的抑制机制在形成最终到达皮层的信号方面起着关键作用。在这里，我们直接探讨了丘脑中两个独立的抑制回路，一个固有于外侧膝状核，另一个起源于相邻的周状核，如何影响传递细胞接受野内的空间和时间整合。我们的主要方法是在体内进行全细胞记录，这使我们能够直接测量突触抑制，以及识别我们记录为X或Y中继细胞或中间神经元的神经元的反应。(1)丘脑中继细胞的感受野继承了视网膜的中心-环绕结构，其输出纯粹是兴奋性的。在视网膜中心和周围，相反对比的刺激引起细胞内相反的反应——“推拉”。丘脑感受野的兴奋性（推）结构是否与局部中间神经元提供的抑制性（拉）相匹配？这些兴奋性和抑制性输入是如何相互作用形成传递到大脑皮层的信息的？(2)在经典感受野（即以视网膜输入为界的区域）之外呈现的刺激具有抑制作用。这种“额外环绕”造成的空间弥漫性抑制被认为起源于卵状旁核。有可能选择性地研究周状突起对中继细胞的影响，因为那里的大多数神经元是双眼的，因此，允许通过非优势眼进行刺激。(3)丘脑反应时间的多样性远远大于视网膜——这是皮层方向选择性模型的核心特征。目前的理论认为，兴奋反应的新延迟是由同号抑制引起的。我们将询问丘脑中间神经元提供的抑制的时间包膜是否能够产生所观察到的兴奋延迟。对大脑正常运作方式的了解，为判断各种疾病导致的变化提供了一个标准，也为测试用于治疗疾病的药物提供了一个模型系统。从这个角度来看，视觉丘脑是一个明显的研究地点；它的功能和解剖结构比任何其他丘脑区域都要清晰。对局部突触机制的更深入了解，可以让我们深入了解疾病期间出现问题的过程。例如，这里提出的工作直接与弱视研究的中心主题有关，即检查异常视觉经验如何导致中央处理的变化。

DESCRIPTION (provided by applicant): The main route from the retina to the visual cortex is through the lateral geniculate nucleus of the thalamus. While retinal input drives thalamic relay cells to fire and outlines their receptive fields, as yet undefined suppressive mechanisms in the thalamus play critical roles in shaping the signals that ultimately reach cortex. Here we explore directly the means by which two separate inhibitory circuits in the thalamus, one intrinsic to the lateral geniculate and the other originating in the adjacent perigeniculate nucleus, influence spatial and temporal integration within the relay cell's receptive field. Our main approach is whole-cell recording in vivo, which allows us to measure synaptic inhibition directly as well as to identify the neurons whose responses we record as X or Y relay cells or interneurons. (1) The receptive fields of thalamic relay cells inherit their center-surround structure from the retina, whose output is purely excitatory. In the retinal center and surround, stimuli of the reverse contrast evoke intracellular responses of the opposite sign -"push-pull". Is the excitatory (push) structure of the thalamic receptive field routinely matched by inhibition (pull) provided by local interneurons? How do these excitatory and inhibitory inputs interact to shape the information transmitted to cortex? (2) Stimuli presented beyond the classical receptive field, that is, the region bounded by retinal input, have a suppressive effect. Spatially diffuse suppression from this "extra surround" is thought to originate in the perigeniculate nucleus. It will be possible to study the influence of the perigeniculate on relay cells selectively because most neurons there are binocular, thus, permitting stimulation via the non-dominant eye. (3) Diversity in response timing in thalamus is far greater than in retina--a feature central to models of cortical direction selectivity. Current theory holds that the novel delays in excitatory responses result from same-sign inhibition. We will ask whether or not the temporal envelopes of inhibition provided by thalamic interneurons are capable of producing the observed delays in excitation. Knowledge of how the brain operates normally provides a standard against which to judge changes that result from various disorders, as well as a model system on which to test drugs developed to treat illness. From this perspective, the visual thalamus is an obvious site to study; its function and anatomy are better resolved than any other thalamic region. A deeper understanding of local synaptic mechanisms provides insight into processes that go awry during disease. For example, the work proposed here bears directly on a central theme in research on amblyopia, the examination of how abnormal visual experience leads to changes in central processing.