Altered norepinephrine transmission after spatial learning impairs sleep-mediated memory consolidation in rats

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 and may importantly contribute to sleep-mediated memory consolidation. The NE transmission fluctuates with the behavioral and/or brain state and influences associated neural activity. Here, we assessed the effects of altered NE transmission after learning of a hippocampal-dependent task on neural activity and spatial memory in adult male rats. We administered clonidine (0.05 mg/kg, i.p.; n = 12 rats) or propranolol (10 mg/kg, i.p.; n = 11) after each of seven daily learning sessions on an 8-arm radial maze. Compared to the saline group (n = 9), the drug-treated rats showed lower learning rates. To assess the effects of drugs on cortical and hippocampal activity, we recorded prefrontal EEG and local field potentials from the CA1 subfield of the dorsal hippocampus for 2 h after each learning session or drug administration. Both drugs significantly reduced the number of hippocampal ripples for at least 2 h. An EEG-based sleep scoring revealed that clonidine made the sleep onset faster while prolonging quiet wakefulness. Propranolol increased active wakefulness at the expense of non-rapid eye movement (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 hippocampal-cortical communication underlying memory consolidation.

PINK1 knockout rats show premotor cognitive deficits measured through a complex maze

“…This suggests that learning acquisition likely began during the initial 3-day training phase where rats were first exposed to the maze. In fact, learning acquisition has been reported in other studies by the third day of training ( Pistell and Ingram, 2010 ; Pistell et al, 2012 ; Durán et al, 2023 ). We speculate that the observed behavior on days 4 and 5 could have resulted from a decreased intrinsic interest in the ongoing food reward, leading rats to choose maze exploration over obtaining the food reward ( Durán et al, 2023 ).…”

“…In fact, learning acquisition has been reported in other studies by the third day of training (Pistell and Ingram, 2010;Pistell et al, 2012;Durán et al, 2023). We speculate that the observed behavior on days 4 and 5 could have resulted from a decreased intrinsic interest in the ongoing food reward, leading rats to choose maze exploration over obtaining the food reward (Durán et al, 2023). Considering the low number of errors made in the testing phase, a more complex configuration of the maze may be able to discern differences in acquisition learning between the genotypes.…”