| In language communication,cognitive learning,abstract thinking,and decisionmaking,the brain needs to temporarily memorize and deal with the relevant information.This calls for an important function known call as working memory.Working memory,an important basic function of the brain,involves temporal store and the comparisons of information,and then generates the decision signals according to a certain rule.Sustained neuronal activities have been found during the working memory tasks in the prefrontal cortex(PFC)of primates.Deactivation of the prefrontal cortex could significantly lower animals' capabilities of working memory.Previous studies conducted in primates mainly focused on working memory research regarding the memory of only uni-sensory information(e.g.colors or shapes of a visual stimulus).It is unclear whether and how neurons of PFC engage in the working memory task,in which cross-modal cues are involved.Using multi-channels recording and optogenetic method,we investigate the neural activities in the medial prefrontal cortex(mPFC)on rats when they perform a delayed match to sample task about the comparison of visual and auditory spatial locations(DMS,a typical task for testing working memory).We have also analyzed the neuronal activities during the visual-auditory working memory.To complete this task,animals must remember the spatial location of visual cue(left or right)and compare it with the location of the following auditory cue and then make the judgment(go left or right).The results demonstrate that mPFC is critical to the task.When the optogenetic deactivation of mPFC(on five rats in total)occurred during the delay period(the temporal window between the first and the second stimuli)decreased the performance of behavioral tests.The similar decline was found when deactivation occurred in the period of the presentation of auditory stimulus.20 rats were used for electrophysiological studies and a total of 531 task related neurons were recorded.More than half of(68%,361/531)neurons showed sustained discharging activity after visual cues disappeared,which was pretty similar to those found in primates.The prolonged activities from most neurons(73%,264/361)carry important information regarding the judgment of visual spatial location.Not all of neurons who kept firing at the delay period could respond to visual stimuli,suggesting that different neurons may play different roles in the process of working memory.The majority of neurons(82%,230/281)responded to visual stimuli showed obvious directional preference.Further study found that nearly half of neurons(52%,274/531)exhibited the obvious difference during the course of decision-making(may also include auditory stimuli),and that the activity of most(68%,185/274)neurons could reflect or encode the matched or not between visual and auditory locations.These results indicate that when animals performed the working memory tasks,prefrontal neurons can not only temporarily store relevant information,but also form decision making instructions.In this experiment,we have successfully established the behavioral model for testing cross-modal working memory in rats.The similar neurons' firing manner,as is reported in the study of working memory in primates,was found in rats.These studies expand our understanding of the neural mechanism of working memory and provide an important experimental evidences for the establishment of memory related disease models in the future.It also provides a good behavioral task models for testing memory related drug. |
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