Unexpected Rule-Changes in a Working Memory Task Shape the Firing of Histologically Identified Delay-Tuned Neurons in the Prefrontal Cortex

Abstract

Summary: Working memory-guided behaviors require memory retention during delay periods, when subsets of prefrontal neurons have been reported to exhibit persistently elevated firing. What happens to delay activity when information stored in working memory is no longer relevant for guiding behavior? In this study, we perform juxtacellular recording and labeling of delay-tuned (-elevated or -suppressed) neurons in the prelimbic cortex of freely moving rats, performing a familiar delayed cue-matching-to-place task. Unexpectedly, novel task-rules are introduced, rendering information held in working memory irrelevant. Following successful strategy switching within one session, delay-tuned neurons are filled with neurobiotin for histological analysis. Delay-elevated neurons include pyramidal cells with large heterogeneity of soma-dendritic distribution, molecular expression profiles, and task-relevant activity. Rule change induces heterogenous adjustments on individual neurons and ensembles’ activity but cumulates in balanced firing rate reorganizations across cortical layers. Our results demonstrate divergent cellular and network dynamics when an abrupt change in task rules interferes with working memory. : Ozdemir et al. perform juxtacellular recording and labeling of delay-tuned neurons in rats performing a working memory task. They show that these cells are heterogeneous in molecular expression and somato-dendritic organization. Unexpected change of the task rule diversely adjusts firing activity of the delay-tuned neurons and prefrontal networks. Keywords: the medial prefrontal cortex, working memory, adaptive cognitive control, memory delay, cellular heterogeneity, juxtacellular labeling