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的外侧膝状体核。虽然视网膜输入驱动丘脑中继细胞放电并勾勒出它们的感受野，但丘脑中尚未确定的抑制机制在塑造最终到达皮层的信号方面起着关键作用。在这里，我们直接探索的手段，其中两个独立的抑制电路在丘脑，一个内在的外侧膝状体和其他起源于相邻的周膝状体核，影响中继细胞的感受野内的空间和时间的整合。我们的主要方法是体内全细胞记录，这使我们能够直接测量突触抑制，并识别我们记录为X或Y中继细胞或中间神经元的神经元。(1)丘脑中继细胞的感受野继承了视网膜的中心-环绕结构，其输出是纯兴奋性的。在视网膜中心和周围，反向对比度的刺激引起相反符号的细胞内反应-“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来塑造传递到皮层的信息的？(2)在经典感受野之外的刺激，即视网膜输入所包围的区域，具有抑制作用。空间弥漫性抑制从这个“额外的包围”被认为是起源于周膝状体核。这将有可能研究的影响，周膝状体上的中继细胞选择性，因为大多数神经元有双眼，因此，允许刺激通过非优势眼。(3)丘脑反应时间的多样性远远大于视网膜--这是皮质方向选择性模型的核心特征。目前的理论认为，兴奋性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络是否能够产生所观察到的兴奋延迟。大脑如何正常运作的知识提供了一个判断各种疾病引起的变化的标准，以及一个测试开发用于治疗疾病的药物的模型系统。从这个角度来看，视觉丘脑是一个明显的研究场所;它的功能和解剖结构比任何其他丘脑区域更好地解决。对局部突触机制的更深入理解提供了对疾病期间出错过程的深入了解。例如，这里提出的工作直接关系到弱视研究的一个中心主题，即检查异常的视觉体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.