Sex-dependent noradrenergic modulation of premotor cortex during decision-making

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.