CIRCUIT ANALYSIS OF PFC-MTL INTERACTIONS IN RATS

项目总结（见说明）： 该项目将采用记录和可逆失活技术相结合，以研究PFC和MTL区域如何在大鼠中相互作用，执行上下文引导的关联任务，该任务在形式上等同于其他项目中用于人类和猴子的测试。在这项任务中，在每次试验中，大鼠将被移动到两个环境背景之一中，这两个环境背景决定了气味刺激和奖励之间的关联。使用多通道四极管，我们将同时记录在MTL区域和PFC区域，并测试特定的假设概述的发展，性质，时间，和协调这些领域的射击模式。 这些研究将测试我们关于大鼠PFC和MTL区域信息处理的总体假设的一般性，并与项目1-3中检查的人类和猴子进行比较。我们还将超越其他实验中识别神经元活动的功能特性，同时 在学习期间和学习之后，在一个区域记录，同时可逆地使另一个区域短暂失活。 可逆失活将使用flocalypmuscimoi和最先进的光学沉默方法来完成，这些方法允许解剖学识别区域的毫秒级分辨率。这些实验将检验在一个区域正常观察到的放电模式是否依赖于另一个区域。例如，我们将测试的假设，即在学习过程中，在PFC的背景一般表示的发展取决于特定的MTL区域;是否，在试验学习后，特定的上下文表示的产生在后嗅/内侧内嗅皮层取决于PFC;以及是否特定的表示的第二个元素的条件关联在PFC的产生取决于嗅周皮层。这些和其他特定的测试将提供PFCMTL电路中区域之间因果关系的证据，为项目6中的计算建模提供关键证据。该项目将密切平行于项目5，该项目检查大鼠执行类似的上下文引导的空间迷宫任务中PFC-MTL相互作用的性质，从而允许将PFC-MTL处理非空间记忆与海马空间记忆的大型文献进行直接比较。

PROJECT SUMMARY (See Instructions): This project will employ a combination of recording and reversible inactivation techniques to examine how PFC and MTL areas interact in rats performing a context-guided association task that is formally equivalent to the test used in humans and monkeys in other projects. In this task, on each trial a rat will be move into one of two environmental contexts that conditions associations between odor stimulis and rewards. Using multichannel tetrodes, we will record simultaneously in an MTL area and a PFC area, and test specific hypotheses outlined about the development, nature, timing, and coordination of firing patterns in these areas. These studies will test the generality of our overall hypotheses about information processing in PFC and MTL areas in rats as compared to those in humans and monkeys examined in Projects 1-3. We will also go beyond identifying functional properties of neuronal activity in other experiments by simultaneously recording in one area while reversibly inactivating another area for brief periods during and after learning. Reversible inactivation will be accomplished using florescent muscimoi and by state-of-the-art optical silencing methods that allow millisecond resolution of anatomically identified areas. These experiments will provide tests of whether firing patterns normally observed in one area depend on the other. For example, we will test the hypothesis that, during learning, the development of context general representations in PFC depend on specific MTL areas; whether, within trials following learning, the generation of specific context representations in postrhinal/medial entorhinal cortex depends on PFC; and whether the generation of specific representations of the second element on a conditional association in PFC depends on perirhinal cortex. These and other specific tests will provide evidence on causal relations among areas within PFCMTL circuitry, providing key evidence for computational modeling in Project 6. This project will closely parallel Project 5, which examines the nature of PFC-MTL interactions in rats performing a similar context guided spatial maze task, thus allowing direct comparisons that link the PFC-MTL processing of non-spatial memorties with the large literature on hippocampal spatial memory.