Parallel processing of working memory and temporal information by distinct types

It is unclear how different types of cortical projection neurons work together to support diverse cortical functions. We examined the discharge characteristics and inactivation effects of intratelencephalic (IT) and pyramidal tract (PT) neurons—two major types of cortical excitatory neurons that project to cortical and subcortical structures, respectively—in the deep layer of the medial prefrontal cortex in mice performing a delayed response task. We found stronger target-dependent firing of IT than PT neurons during the delay period.

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Fig: mPFC inactivation impairs behavioral performance: a The experimental setting (custom-created image). Head-fixed mice performed a delayed match-to-sample task. b Schematic for a left-target trial. Mice obtained a water reward by choosing the lick port presented during the sample phase (target) before a delay period. c Schematic (left) and a coronal brain section (representative of six mice; right) showing cannula tracks and the spread of fluorescein (green) in the mPFC. PL prelimbic cortex, IL infralimbic cortex. Scale bar, 500 μm. d–f Effects of mPFC inactivation on behavior under the 4-s fixed-delay condition. dLicking responses during example sessions with bilateral ACSF (left) or muscimol (right) infusions into the mPFC. Each line is one trial and each dot represents a lick (green, right; purple, left). Error, wrong target choice; miss, no choice. Trials are grouped according to trial type (correct, error, and miss) and target (left versus right lick port). e, f Mean (±SEM across six WT mice) fractions of correct (left), error (middle), and miss (right) trials (e) as well as lick rates during the delay period (f) following ACSF, muscimol (Mus), and no-drug (Ctrl) infusions. Thin lines, individual animal data. *p < 0.05, ***p < 0.001 (one-way repeated measures ANOVA followed by Bonferroni’s post hoc tests).

We also found the inactivation of IT neurons, but not PT neurons, impairs behavioral performance. In contrast, PT neurons carry more temporal information than IT neurons during the delay period. Our results indicate a division of labor between IT and PT projection neurons in the prefrontal cortex for the maintenance of working memory and for tracking the passage of time, respectively.

Bae, J.W., Jeong, H., Yoon, Y.J. et al. Parallel processing of working memory and temporal information by distinct types of cortical projection neurons. Nat Commun 12, 4352 (2021). https://doi.org/10.1038/s41467-021-24565-z

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