Working memory(WM)is essential for cognition by allowing active retention of behaviorally relevant information over a short duration,known as the delay period.Previous studies have shown that the prefrontal cortex(PFC)is crucial for WM,because perturbation of PFC activity impaired WM and WM-related activity was observed during the delay period in neurons of dorsallateral PFC(DL-PFC)in primates and medial PFC(mPFC)in rodents.Nevertheless,the functional role of PFC delay-period activity in WM remains unclear.Memory retention and attentional control are leading candidates.However,PFC is also critical for other brain functions and has been suggested to be important for inhibitory control,decision making,or motor selection.These roles cannot be distinguished by a delayed-response task,in which decision making precedes the delay period.In addition,traditional methods for perturbing neural activity,including transcranial magnetic stimulation and electrical stimulation,do not provide the temporal resolution and cell-type specificity required for delineating the functional role of PFC delay-period activity in WM.These issues were addressed in the present study(Liu,et al.,2014,Science)by using a WM task with a delay period designed to temporally separate memory retention from other functions and optogenetic approaches to bidirectionally manipulate mPFC activity of excitatory and inhibitory neurons during the delay period.We optogenetically suppressed or enhanced activity of pyramidal neurons in mouse mPFC during the delay period.Behavioral performance was impaired during the learning phase but not after the mice were well-trained.Delay-period mPFC activity appeared to be more important in memory retention than in inhibitory control,decision making,or motor selection.Furthermore,endogenous delay-period mPFC activity showed more prominent modulation that correlated with memory retention and behavioral performance.Thus,properly regulated mPFC delay-period activity is critical for information retention during learning of a WM task.I will also share preliminary result on optogenetic and electrophysiological results from a sensory region in learning and well-trained phases of the WM task.