Sex-dependent noradrenergic modulation of premotor cortex during decision making
- University of Massachusetts Amherst, United States
Abstract
Rodent premotor cortex (M2) integrates information from sensory and cognitive networks for action planning during goal-directed decision making. M2 function is regulated by cortical inputs and ascending neuromodulators, including norepinephrine (NE) released from the locus coeruleus (LC). LC-NE has been shown to modulate the signal to noise ratio of neural representations in target cortical regions, increasing the salience of relevant stimuli. Using rats performing a two-alternative forced choice task after administration of a β noradrenergic antagonist (propranolol), we show that β noradrenergic signaling is necessary for effective action plan signals in anterior M2. Loss of β noradrenergic signaling results in failure to suppress irrelevant action plans in anterior M2 disrupting decoding of cue related information, delaying decision times, and increasing trial omissions, particularly in females. Furthermore, we identify a potential mechanism for the sex bias in behavioral and neural changes after propranolol administration via differential expression of β2 noradrenergic receptor RNA across sexes in anterior M2, particularly on local inhibitory neurons. Overall, we show a critical role for β noradrenergic signaling in anterior M2 during decision making by suppressing irrelevant information to enable efficient action planning and decision making.
Data availability
Data analyzed during this study are included in the supporting file.
Article and author information
Author details
Funding
National Institute of Mental Health (R00MH104716)
- Elena M Vazey
National Institute of Mental Health (F31MH131348)
- Ellen M Rodberg
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All procedures were approved by the Institutional Animal Care and Use Committee at the University of Massachusetts Amherst (#2018-0080) in accordance with the guidelines described in the US National Institutes of Health Guide for the Care and Use of Laboratory Animals (National Research Council 2011). All surgery was performed under isoflurane anesthesia, and every effort was made to minimize suffering.
Copyright
© 2023, Rodberg et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Sex-dependent noradrenergic modulation of premotor cortex during decision making
eLife 12:e85590.
https://doi.org/10.7554/eLife.85590
Further reading
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When holding visual information temporarily in working memory (WM), the neural representation of the memorandum is distributed across various cortical regions, including visual and frontal cortices. However, the role of stimulus representation in visual and frontal cortices during WM has been controversial. Here, we tested the hypothesis that stimulus representation persists in the frontal cortex to facilitate flexible control demands in WM. During functional MRI, participants flexibly switched between simple WM maintenance of visual stimulus or more complex rule-based categorization of maintained stimulus on a trial-by-trial basis. Our results demonstrated enhanced stimulus representation in the frontal cortex that tracked demands for active WM control and enhanced stimulus representation in the visual cortex that tracked demands for precise WM maintenance. This differential frontal stimulus representation traded off with the newly-generated category representation with varying control demands. Simulation using multi-module recurrent neural networks replicated human neural patterns when stimulus information was preserved for network readout. Altogether, these findings help reconcile the long-standing debate in WM research, and provide empirical and computational evidence that flexible stimulus representation in the frontal cortex during WM serves as a potential neural coding scheme to accommodate the ever-changing environment.
