Working memory (WM) is a critical cognitive ability of actively maintaining and manipulating information over a short “delay period” of seconds, after the stimulus cue but before behavioral action. Examples of WM include memorizing telephone number before dialing it, arithmetic calculation, mentally organizing details in planning a trip, etc. During WM tasks, changes in activities were found in many brain areas during the delay period. Such “persistent delay-period activity” was currently thought as the neural mechanism underlying WM. However the functional significance of such activity remains controversial. Moreover, the neural mechanism in generating the persistent activity is still unknown. 

  To tackle the problems, we utilized optogenetic and electrophysiological methods in head-fixed mice. Furthermore, we focused on olfactory WM tasks that allow temporal separation of memory retention from decision making, for clear interpretation of optogenetic and recording results. In medial prefrontal cortex (mPFC) (Liu, et al., Science, 2014), we have found that optogenetic manipulation of neuronal activity of pyramidal neurons during memory retention period impaired the performance of working memory task, during the learning phase but not in well-trained mice. Silencing mPFC activity in decision-making periods, however, only impaired WM performance in later phase of learning and well-trained phases. Therefore through learning experience, brain circuit undergoes dynamical shift in functional roles in WM task. 

    Currently we are actively studying the functional roles of other brain regions in olfactory WM tasks, as well as how the delay-period activity is generated. Our research aims to uncover the neural circuit mechanism underlying WM in the brain.

LI Chengyu, Ph.D.

Senior Investigator