Imaging neural activity in the rat frontal cortex during short-term memory

描述（由申请人提供）：已经提出短期记忆是由新皮层的前额叶和顶叶区域内的神经元网络的持续活动编码的，然而存储的精确机制仍然存在争议。由于短期记忆在人类认知功能中的重要性及其随年龄和神经系统疾病的下降，短期记忆的神经基础的识别一直是重要的研究工作的主题。关于短时记忆在大脑皮层的储存，有两种假说：持续性神经活动假说和顺序性神经活动假说。为了区分这两种假设，我将研究大鼠前额叶和顶叶皮层在短期记忆中的神经动力学。大鼠在测量短期记忆的皮质动力学方面有许多明显的优势。首先，老鼠可以接受涉及短期记忆的认知任务的训练。第二，大鼠适合于测量神经活动的先进技术，例如遗传编码钙传感器的体内双光子显微镜（体内成像）。体内成像能够同时记录许多神经元，这对于区分持续性神经活动和顺序性神经活动至关重要。 我的实验方法分为三个目标。首先，我的目标是优化和表征一种新的系统，我在自愿头枕在体内成像开发。这种方法允许在短期记忆任务中训练的大鼠暂时头部约束自己，同时记录皮质动力学。在目标2中，我将使用这种技术来记录记忆引导定向任务期间大鼠额叶皮层的活动。在目标3中，我在相同的条件下记录大鼠顶叶皮层的神经活动。在记忆引导的运动任务中，额顶叶回路的持续活动和顺序活动都被预测。在这项任务中，在两个区域进行记录，应该可以让我批判性地评估这两种被提出的皮质动力学和短期记忆之间的关系。

DESCRIPTION (provided by applicant): It has been proposed that short-term memory is encoded by ongoing activity of neuronal networks within the prefrontal and parietal regions of the neocortex, however the precise mechanism of storage remains controversial. Due to the importance of short-term memory in human cognitive function and its decline with age and neurological disorders, the identification of the neural basis of short-term memory has been a subject of significant research efforts. Two hypotheses have been proposed for short-term memory storage in the cerebral cortex, persistent neural activity and sequential neural activity. In order to discriminate between these two hypotheses, I will study the neural dynamics in the rat prefrontal and parietal cortices during short-term memory. Rats offer a number of distinct advantages for the measurement of cortical dynamics that underlie short-term memory. First, rats can be trained in cognitive tasks that involve short-term memory. Second, rats are amenable to advanced techniques for the measurement of neural activity, such as in vivo two-photon microscopy of genetically encoded calcium sensors (in vivo imaging). In vivo imaging enables the recording of many neurons simultaneously, which is crucial to discriminate between persistent neural activity and sequential neural activity. My experimental approach is divided into 3 aims. First I aim to optimize and characterize a novel system that I developed for in vivo imaging during voluntary head restraint. This approach allows for rats trained in short-term memory tasks to temporarily head restrain themselves to while cortical dynamics are recorded. In Aim 2 I will use this technique to record activity in the rat frontal cortex during a memory guided orienting task. In Aim 3 I record neural activity in the rat parietal cortex under the same conditions. Both persistent activity and sequential activity have been predicted in frontoparietal circuits during memory guided movement tasks. Recording in two regions during this task should allow me to critically evaluate the relationship between these two proposed forms of cortical dynamics and short-term memory.