The role of NMDA receptor-dependent activity of noradrenergic neurons in attention, impulsivity and exploratory behaviors

Abstract

Activity of the brain's noradrenergic (NA) neurons plays a major role in cognitive processes, including the ability to adapt behavior to changing environmental circumstances. Here, we used the NR1DbhCre transgenic mouse strain to test how NMDA receptor-dependent activity of NA neurons influenced performance in tasks requiring sustained attention, attentional shifting and a trade-off between exploration and exploitation. We found that the loss of NMDA receptors caused irregularity in activity of NA cells in the locus coeruleus and increased the number of neurons with spontaneous burst firing. On a behavioral level, this was associated with increased impulsivity in the go/no-go task and facilitated attention shifts in the attentional set-shifting task. Mutation effects were also observed in the two-armed bandit task, in which mutant mice were generally more likely to employ an exploitative rather than exploratory decision-making strategy. At the same time, the mutation had no appreciable effects on locomotor activity or anxiety-like behavior in the open field. Taken together, these data show that NMDA receptor-dependent activity of brain's NA neurons influences behavioral flexibility.