Altered Norepinephrine Transmission after Spatial Learning Impairs Sleep-Mediated Memory Consolidation in rats

Abstract

Abstract The therapeutic use of noradrenergic drugs makes the evaluation of their effects on cognition of high priority. Norepinephrine (NE) is an important neuromodulator for a variety of cognitive processes, including memory. The NE transmission fluctuates with the behavioral state and influences associated neural activity. Here, we addressed the role of NE during a post-learning period in the sleep-mediated mechanisms of memory consolidation. We treated adult male rats with clonidine (0.05 mg/kg, i.p.), propranolol (10 mg/kg, i.p.), or saline after each of seven daily learning sessions on an 8-arm radial maze. We monitored the prefrontal EEG and population activity in the hippocampus for 2h after the drug administration. Both drugs made spatial learning less efficient and dramatically reduced the occurrence of hippocampal ripples at least for 2h post-injection. Clonidine made the sleep onset faster while prolonging quiet wakefulness. Propranolol increased active wakefulness at the expense of NREM sleep. Clonidine reduced the occurrence of slow oscillations (SO) and sleep spindles during NREM sleep and altered the temporal coupling between SO and sleep spindles. Thus, pharmacological alteration of NE transmission produced a suboptimal brain state for memory consolidation. Our results suggest that the post-learning NE contributes to the efficiency of ripple-associated memory trace replay and hippocampal-cortical communication underlying memory consolidation.