Sex differences in noradrenergic regulation of the medial prefrontal cortex in mice

Females have a larger locus coeruleus → medial prefrontal cortex circuit than males. Basal norepinephrine levels and adrenergic receptor gene expression levels are similar in the medial prefrontal cortex of male and female mice. Norepinephrine broadly increases glutamate release onto medial prefrontal cortex pyramidal neurons in male mice. In female mice, norepinephrine-induced glutamate release is restricted to prelimbic cortex layer 5 and infralimbic cortex layer 2/3 pyramidal neurons. Norepinephrine altered medial prefrontal cortex-dependent cognitive behaviors (reversal learning and episodic memory) in mice, but there were no sex differences in its effects.