Coordinated forms of noradrenergic plasticity in the locus coeruleus and primary auditory cortex

The cerebral cortex is plastic and represents the world according to the significance of sensory stimuli. However, cortical networks are embodied in complex circuits, including neuromodulatory systems such as the noradrenergic locus coeruleus, providing information about internal state and behavioral relevance. Although norepinephrine is important for cortical plasticity, it is unknown how modulatory neurons themselves respond to changes of sensory input. We examined how locus coeruleus neurons are modified by experience and the consequences of locus coeruleus plasticity for cortical representations and sensory perception. We made whole-cell recordings from rat locus coeruleus and primary auditory cortex (A1), pairing sounds with locus coeruleus activation. Although initially unresponsive, locus coeruleus neurons developed and maintained auditory responses afterwards. Locus coeruleus plasticity induced changes in A1 responses lasting at least hours and improved auditory perception for days to weeks. Our results demonstrate that locus coeruleus is highly plastic, leading to substantial changes in regulation of brain state by norepinephrine.