Processing of complex stimuli in the primary sensory cortex.

描述(申请人提供)：了解大脑如何处理复杂的信号是感觉神经科学的基本目标之一。这些研究要求人们能够将感觉神经元对诱发它们的复杂感觉刺激的反应联系起来。在胡须初级体感系统(S1)中，这些研究传统上被证明具有挑战性，原因有两个：1)将时空复杂的刺激独立地传递到多个胡须在技术上是困难的；2)S1的放电频率通常非常低，以至于不可能获得构建准确的感受野估计所需的数据量。该项目通过开发一种新的多晶须刺激器系统来克服这两个限制，该系统能够刺激比以前探索的更高维度的空间。此外，我们还开发了新的接受场估计方法，该方法依赖于亚阈值信息而不是尖峰。这些进步使我们能够在几分钟内收集到通过传统的细胞外记录需要数小时收集的数据量。此外，我们的方法能够检测到经典使用的依赖于尖峰的接受场分析无法检测到的非线性现象。我们的研究将是第一次研究在躯体感觉皮质的皮质柱中处理时空复杂刺激的突触机制。这项研究将告诉我们感觉皮层如何处理复杂的刺激信息，以及大脑如何在感觉世界中检测复杂的结构特征。通过使用全细胞记录和我们新的多胡须刺激器系统，我们将研究L4如何整合复杂的刺激，这在亚阈值水平上驱动反应高达多个胡须。我们开发了非线性分析方法，以表明L4以非线性的方式整合了多个晶须输入。这些非线性对于克服复杂刺激期间L4的环绕抑制可能是重要的。接下来，我们利用我们的多晶须刺激器系统来解决L2/3中神经元的反应特性。具体地说，我们能够解决L2/3使用稀疏编码策略来编码复杂刺激信息的理论。通过使用最大噪声熵模型，我们能够在线计算L2/3神经元的最优刺激，然后将刺激传递回相同的神经元，从而使其激发。通过驱动L2/3的尖峰反应，我们将能够确定L2/3是否采用稀疏编码机制，以及L2/3对哪些刺激特征敏感。最后，我们将展示L5/6神经元对于编码感觉环境中的结构特征可能是重要的。我们将使用我们新开发的感受场分析技术来探索S1深层神经元在时空上复杂的感受场。这些感受场将告诉我们，深层神经元是否对提取结构特征可能是重要的，这些结构特征由胡须之间的时间延迟编码。我们的研究将有助于推动该领域对皮层微电路如何处理复杂和自然的信息有一个统一的理解。

DESCRIPTION (provided by applicant): Understanding how the brain processes complex signals is one of the fundamental goals of sensory neuroscience. These studies require one to be able to correlate the responses of sensory neurons to the complex sensory stimuli that elicited them. In the whisker primary somatosensory system (S1), these studies have traditionally proven challenging for two reasons: 1) Delivering spatiotemporally complex stimuli to multiple whiskers independently has been technically difficult, and 2) firing rates in S1 are often so low that it is not possible to acquire the amount of data needed to construct accurate receptive field estimates. This project has overcome these two constraints by developing a new multi-whisker stimulator system capable of stimulating a higher dimensional space than previously explored. Additionally, we have developed novel receptive field estimation methods that rely on subthreshold information rather than spikes. These advances allow us to collect in minutes the amount of data that would have taken hours to collect through traditional extra-cellular recordings. Furthermore, our method is capable of detecting nonlinear phenomena that are not detected by classically used receptive field analysis relying on spikes. Ours will be the first study that investigates the synaptic mechanisms underlying the processing of spatiotemporally complex stimuli in a cortical column of somatosensory cortex. This study will inform us how sensory cortices process complex stimulus information, as well as how the brain detects complex structural features in the sensory world. Through the use of whole- cell recordings and our new multi-whisker stimulator system, we will investigate how L4 integrates complex stimuli, which at the subthreshold level drives responses up to multiple whiskers away. We develop nonlinear analysis methods to show that L4 integrates multi-whisker inputs in a nonlinear fashion. These nonlinearities may be important for overcoming surround suppression in L4 during complex stimuli. Next we take advantage of our multi-whisker stimulator system to address response properties of neurons in L2/3. Specifically we are able to address the theory that L2/3 is using a sparse coding strategy to encode complex stimulus information. Through the use of a maximum noise entropy model, we are able to calculate the optimal stimulus for a L2/3 neuron online, and then deliver the stimulus back to the same neuron, thus making it fire. By driving spiking responses in L2/3 we will be able to determine whether L2/3 is employing a sparse coding regime, as well as what stimulus features L2/3 is sensitive to. Lastly, we will show that L5/6 neurons may be important for encoding structural features in the sensory environment. We will use our newly developed receptive field analysis techniques to probe the spatiotemporally complex receptive fields of deep layer neurons in S1. These receptive fields will inform us whether deeper layer neurons may be important for extracting structural features, encoded by temporal delays between whiskers. Our study will help move the field toward a unified understanding of how cortical microcircuits process complex and naturalistic information.