Processing of complex stimuli in the primary sensory cortex.

描述（由申请人提供）：了解大脑如何处理复杂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的反应与引起它们的复杂感觉刺激联系起来。在须初级体感系统（S1）中，这些研究传统上被证明具有挑战性，原因有两个：1)将时空复杂的刺激单独传递给多个须在技术上是困难的，2)S1的放电率通常很低，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系统克服了这两个限制，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野估计方法，该方法依赖于阈下信息而不是峰值。这些进步使我们能够在几分钟内收集到的数据量，而通过传统的蜂窝外记录需要花费数小时才能收集到。此外，我们的方法能够检测依赖于峰值的经典感受野分析无法检测到的非线性现象。我们将是第一个研究在体感皮层皮层柱中处理时空复杂刺激的突触机制的研究。这项研究将告诉我们感觉皮质如何处理复杂的刺激信息，以及大脑如何检测感官世界中的复杂结构特征。通过使用全细胞记录和我们新的多须刺激系统，我们将研究L4如何整合复杂的刺激，这些刺激在阈下水平上驱动对多个须的反应。我们开发了非线性分析方法来显示L4以非线性方式集成多晶须输入。这些非线性可能对克服复杂刺激下L4的包围抑制很重要。接下来，我们利用我们的多晶须刺激系统来研究L2/3神经元的响应特性。具体来说，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，然后将刺激传递回同一神经元，从而使其放电。通过驱动L2/3的尖峰响应，我们将能够确定L2/3是否采用稀疏编码制度，以及L2/3对什么刺激特征敏感。最后，我们将证明L5/6神经元可能对编码感觉环境中的结构特征很重要。我们将使用我们新开发的感受野分析技术来探测S1深层神经元的时空复杂感受野。这些感受野将告诉我们，深层神经元是否对提取结构特征很重要，这些结构特征是由晶须之间的时间延迟编码的。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信息的统一理解。

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. PUBLIC HEALTH RELEVANCE: Understanding the functional response properties of neurons throughout the depths of a cortical column will allow us to probe the contributions of different layers of the cortex in behavior as well as in disease. In particular, deep layer neurons involved in striatal and callosal circuits have been implicated in epilepsy and Parkinson's and understanding what drives these neurons will provide an invaluable tool for understanding the role of these circuits in disease. This project illuminates the functional response properties of different neurons throughout the cortical layers during complex sensory stimulation, in the specific case of the primary somatosensory cortex.