Abstract
Medial prefrontal cortex (mPFC) activity is fundamental for working memory (WM), attention, and behavioral inhibition; however, a comprehensive understanding of the neural computations underlying these processes is still forthcoming. Towards this goal, neural recordings were obtained from the mPFC of awake, behaving rats performing an odor span task of WM capacity. Neural populations were observed to encode distinct task epochs and the transitions between epochs were accompanied by abrupt shifts in neural activity patterns. Putative pyramidal neuron activity increased earlier in the delay for sessions where rats achieved higher spans. Furthermore, increased putative interneuron activity was only observed at the termination of the delay thus indicating that local processing in inhibitory networks was a unique feature to initiate foraging. During foraging, changes in neural activity patterns associated with the approach to a novel odor, but not familiar odors, were robust. Collectively, these data suggest that distinct mPFC activity states underlie the delay, foraging, and reward epochs of the odor span task. Transitions between these states enable successful performance in dynamic environments placing strong demands on the substrates of working memory.
Significance Statement Working memory capacity is altered in psychiatric disorders including schizophrenia. In the present manuscript, we describe activity states of neurons in medial prefrontal cortex as well-trained rats perform the odor span task, which has been nominated as a task suitable for studying working memory capacity in rodents. Our results demonstrate dynamic and flexible activity patters during different epochs of the task (i.e., the delay period, foraging, reward collection, and after making errors). Our results bolster contemporary theories of the medial prefrontal cortex exhibiting metastable dynamics in complex environments. Disruptions in these dynamics may underlie some cognitive symptoms of schizophrenia, including reduced working memory capacity.
Footnotes
The authors declare no competing interests related to the present work.
This work was supported by a CIHR Open Operating Grant (#125984) and NSERC Discovery Grant to JGH and by the National Institutes of Health grants AA022821, AA023786, and P60-AA007611 to CCL. LA was supported by a Saskatchewan Health Research Foundation Fellowship, NS was supported by the College of Medicine (University of Saskatchewan), AJR was supported by an NSERC CREATE scholarship.
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
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