Abstract
Working memory is the ability to briefly remember and manipulate information after it becomes unavailable to the senses. The mechanisms supporting working memory coding in the primate brain remain controversial. Here we demonstrate that microcircuits in layers 2/3 of the primate lateral prefrontal cortex dynamically represent memory content in a naturalistic task through sequential activation of single neurons. We simultaneously recorded the activity of hundreds of neurons in the lateral prefrontal cortex of macaque monkeys during a naturalistic visuospatial working memory task set in a virtual environment. We found that the sequential activation of single neurons encoded trajectories to target locations held in working memory. Neural sequences were not a mere successive activation of cells with memory fields at specific spatial locations, but an abstract representation of the subject’s trajectory to the target. Neural sequences were less correlated to target trajectories during perception and were not found during working memory tasks lacking the spatiotemporal structure of the naturalistic task. Finally, ketamine administration distorted neural sequences, selectively decreasing working memory performance. Our results indicate that neurons in the lateral prefrontal cortex causally encode working memory in naturalistic conditions via complex and temporally precise activation patterns.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵1 Co-first author;
↵* Co-senior author;
MR, LP, and JCMT planned the experiments. MR and RL trained animals, performed the experiments and conducted data preprocessing including spike sorting. MR and AB analyzed the data, created figures and wrote the paper with help from JCMT and LM. BC developed unique MATLAB code for eye movement classification and analysis. RAG developed code for data preprocessing and contributed essential knowledge of experimental design and data analysis. BC and RAG trained animals to perform eye fixations for eye tracking calibration. MLL collected the ODR dataset. AJS, JCMT, RAG, RL, and MR planned and conducted surgeries. JM contributed to the dimensionality analysis development. MHM contributed to data analysis and analysis planning.
