Cortical Feedback Inhibition

描述（由申请人提供）：突触抑制在塑造神经元群体在空间和时间上的活动以及防止兴奋通过皮层神经元网络不受限制地传播方面发挥关键作用。反馈抑制回路是突触抑制的主要来源，因此在控制过度兴奋中起着非常重要的作用。当抑制性神经元投射到它们从其接收兴奋的神经元群体时，反馈抑制发生。这种回路在皮层区域是典型的，被认为是皮层组织的一般原则。与反馈抑制的解剖学特性的丰富知识相反，人们对这种回路控制神经元网络活动的具体方式知之甚少。这个提议提出了反馈抑制回路控制海马锥体神经元兴奋性的机制，海马是一个兴奋和抑制之间轻微失衡可导致癫痫样活动的结构。我们的初步数据表明，至少有两个独立的反馈途径抑制海马锥体细胞。一条通路优先被锥体细胞的低尖峰频率（< 10 Hz）激活，而另一条通路在锥体细胞的较高尖峰频率（>10 Hz）下被激活。此外，其中一条通路抑制锥体细胞的索马，而另一条通路抑制锥体细胞的树突，这表明它们可能影响不同的兴奋性输入。这项研究将揭示一个简单但强大和无处不在的神经元回路控制海马兴奋的机制，从而有助于开发旨在预防皮质区过度兴奋和癫痫发生的治疗方法。此外，阐明基本电路的功能特性，如反馈抑制，将允许，从长远来看，理解决定更大的神经元网络的空间和时间活动模式的机制。

DESCRIPTION (provided by applicant): Synaptic inhibition exerts a crucial function in shaping the activity of neuronal populations in space and time and in preventing excitation to spread unrestrained through networks of cortical neurons. Feedback inhibitory circuits are a major source of synaptic inhibition and thus, play a very important role in the control of hyperexcitability. Feedback inhibition occurs when inhibitory neurons project to the population of neurons from whom they receive excitation. Such circuits are stereotypical in cortical areas and are regarded as a general principle of cortical organization. In contrast to the wealth of knowledge on the anatomical properties of feedback inhibition, the specific means by which this circuit controls the activity of networks of neurons is poorly understood. This proposal addresses the mechanism by which feedback inhibitory circuits control the excitability of pyramidal neurons in the hippocampus, a structure where a slight imbalance between excitation and inhibition can lead to epileptiform activity. Our preliminary data suggest that at least two independent feedback pathways inhibit hippocampal pyramidal cells. One pathway is preferentially activated by low spiking frequencies (< 10 Hz) while the other is activated at higher spiking frequencies (>10 Hz) of pyramidal cells. Furthermore, one pathway inhibits the soma while the other inhibits the dendrites of pyramidal cells, suggesting that they may affect different sets of excitatory inputs. This study will reveal the mechanism by which a simple but powerful and ubiquitous neuronal circuit controls excitation in the hippocampus and may thus contribute to the development of therapies aimed a preventing hyperexcitability and epileptogenesis in cortical areas. Furthermore, elucidating the functional properties of elementary circuits, like feedback inhibition, will allow, in the long term, to understand the mechanisms that determine the spatial and temporal activity patterns of larger networks of neurons.