Etudes des mécanismes de l'adaptation et des relations interneuronales au cortex.

** *在上一个周期，我的实验室*研究了两个主题。A)适应对视觉皮层*偏好刺激变化的影响；我们的发现为探索神经元和神经网络的可塑性提供了机会。B)形成连接体的神经元之间的功能关系。这个话题提出了一个对神经元信号进行编码的过程。我们的研究计划旨在进一步发展上述创新课题，以了解中枢神经系统可塑性的基本机制和群体编码的动态。我们提出的计划涉及两个最热门的主题：连接体的可塑性和动力学。实验是在麻醉的动物身上进行的。电极基质被放入皮层。将调查*以下具体主题。***A)初始刺激对后续刺激引起的反应的影响。刺激会留下痕迹。*在初始阶段，我们使用两种类型的刺激。第一个条件作用短刺激是恒定的，即表现出相同的性质，第二个条件作用刺激（相同类型）投射出可变的性质，如方向。条件反射刺激在预定的间隔之后是测试刺激。假设是每个条件反射刺激如何影响对测试刺激的反应？取向调节曲线的峰值是否发生了变化，也就是说，细胞是否改变了它们的选择性？细胞的兴奋性动态变化？考察了这一“记忆轨迹”的时间进程。根据记录的神经元之间的节律性和协同性来分析反应。***B)血清素/氟西汀*(S/F)和氯胺酮的作用。自适应移动了方向调谐曲线的峰值，即单元获得了新的*选择性。S/F促进了这种适应性诱导的可塑性。初步数据显示氯胺酮可以对抗S/F效应。提示S/F*可降低GABA水平，从而通过提高BDNF*的利用率来提高成人大脑的可塑性。我们将通过环曲素阻断BDNF的主要受体：TrkB来研究BDNF的作用。药物是局部应用的。***C)皮质层的适应性。*我们发现LGN细胞抵抗适应。第4层单元（颗粒）主要由LGN驱动。问题来了，第2、3、5、6层的皮质细胞是如何改变它们的最佳方向的？适应诱导的可塑性是否内在地发生在颗粒层上和颗粒层下？这个问题引出了我们的第四个目标。***D)神经元间功能关系的调节。交叉相关图技术揭示了神经元之间的功能关系。它公开了一个连接体。细胞对连接组的忠诚取决于刺激。工作假设是确定除了经典的神经元选择性外，连接组选择性信号是否也有相关的变化。另外17区的连接体是如何在18区的读取的？**

* **During the last cycle my lab*investigated two themes. A) The influence of adaptation on changes of*preferred stimulus in visual cortex; our findings point to opportunities to explore plasticity of*neurons and neuronal networks. B) The functional*relationships between neurons forming a connectome. This topic suggests*a process of encoding neuronal signals.***Our research program aims to further develop*the above innovative topics in order to understand fundamental *mechanisms of plasticity and the dynamics of population encoding in the CNS. Our proposed program deals with the two hottest*topics: plasticity and dynamics of connectomes. ***Experiments are carried out on*anesthetized animals. Electrode matrices are lowered into the cortex. The*following specific subjects will be investigated.***A) Influence of an initial stimulus upon responses evoked*by a following stimulus. Stimuli leave a trace.*In the initial phase we apply two types of stimuli. The first conditioning short stimulus is constant, that is,*exhibiting an identical property, the second conditioning*stimulus (same type) projects a variable property e.g.orientations. Conditioning stimuli are*followed at a predetermined interval by a test stimulus. The hypothesis is how each of the*conditioning stimuli affects the responses to the test stimulus? Does the peak of the orientation tuning curve shifts, i.e., do cells*change their selectivity? Do dynamic of cell's excitability change? The time course of this “memory trace” is examined. Responses are analyzed in term of rhythmicity and*synergy between recorded neurons. ***B) Effects of serotonin/Fluoxetine*(S/F) and Ketamine. Adaptation shifts orientation tuning curve peaks, i.e., units acquire a new*selectivity. This adaptation-induced plasticity is facilitated*by S/F. Preliminary data show that ketamine opposes S/F effects. It is suggested that S/F*lower GABA levels, which increases plasticity in adult brains by enhancing BDNF*availability. We shall investigate the role of BDNF by blocking its*primary receptor: TrkB, with Cyclotraxine. Drugs are applied locally.***C) Adaptation in cortical layers.*We showed that cells of the LGN resist adaptation. Layer 4 units (granular) are mostly driven by LGN. The question arises, how do cortical cells of layers 2,3, 5,6 change their*optimal orientation? Does adaptation-induced plasticity occur intrinsically within supra- and*infra-granular layers? This question leads*to our fourth goal.***D) Modulation of functional*relationships between neurons. The functional relationships between neurons*are revealed by the cross correlogram techniques. It discloses a connectome. The allegiance of*cells to a connectome changes depending upon stimulus. The *working hypothesis is to determine if in addition to classical neuronal selectivity, there is a correlating change in connectome*selectivity signaling. In addition how connectome in area 17 is read in area 18?**