β-adrenergic Receptor Activity in the Hippocampal Dentate Gyrus Participates in Spatial Learning and Memory Impairment in Sleep-deprived Rats

Sleep deprivation (SD) leads to cognitive impairment, especially hippocampus-dependent learning and memory (L&M). The hippocampal dentate gyrus (DG) is the key structure involved in spatial L&M while long-term potentiation (LTP) is an important cellular mechanism responsible for L&M. Physiological and behavioral evidences support the hypothesis that norepinephrine (NE) and beta-adrenoceptors (beta-AR) may play an important role in regulating L&M, including LTP. However, it is enigmatic how beta-AR influences the LTP disruption or memory impairment under SD circumstances. In the present study, the rats were subjected to SD for 18 h per day for 21 consecutive days and cognitive capacity was assessed by the Morris water maze (MWM) test. We examined the extracellular concentration of NE in the DG using in vivo brain microdialysis and HPLC analysis. The amplitudes of field excitatory postsynaptic potential (fEPSP) were subsequently measured in the DG during MWM test in freely moving conscious rats. The extracellular concentrations of NE and fEPSP amplitudes in the DG were significantly increased during MWM test, while these responses were suppressed in SD rats. When fEPSP amplitudes in the DG were measured after local injection of isoproterenol (an agonist of beta-AR), SD rats significantly alleviated the fEPSP impairment and rescued deficits of spatial L&M. In addition, the reduced expression of N-methyl-Daspartate (NMDA) and a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors in SD rats significantly increased by activation of beta-AR by isoproterenol in the DG. In conclusion, we propose that beta-adrenergic signaling can improve memory impairment in sleep-deficient rats by regulating synaptic efficiency and glutamatergic receptor expression.

Automated summary

Sleep deprivation can lead to cognitive impairment, specifically affecting hippocampus-dependent learning and memory. Studies have shown that beta-adrenergic signaling plays a crucial role in regulating spatial learning and memory, with activation of beta-AR improving memory deficits in sleep-deprived rats.