Sex-dependent noradrenergic modulation of premotor cortex during decision making

Rodent premotor cortex (M2) integrates information from sensory and cognitive networks for action selection and 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 regions prior to decision execution, to increase the salience of relevant stimuli. Using rats performing a two-alternative forced choice task after administration of a β adrenergic antagonist (propranolol), we show that action planning in M2 is mediated by β adrenergic signaling. Loss of β adrenergic signaling results in failure to suppress irrelevant action plans in M2 that disrupts decoding of cue related information, delays decision times, and increases 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 receptors across sexes, particularly on local inhibitory neurons. Overall, we show a critical role for β adrenergic signaling in M2 during decision making by suppressing irrelevant information to enable efficient action planning and decision execution.