Hippocampal synaptic plasticity and spatial learning are impaired in a rat model of sleep fragmentation.
Sleep fragmentation, a symptom in many clinical disorders, leads to cognitive impairments. To investigate the mechanisms by which sleep fragmentation results in memory impairments, rats were awakened once every 2 min via 30 s of slow movement on an automated treadmill. Within 1 h of this sleep interruption (SI) schedule, rats began to sleep in the 90-s periods without treadmill movement. Total non-rapid eye movement sleep (NREM) sleep time did not change over the 24 h of SI, although there was a significant decline in rapid eye movement sleep (REM) sleep and a corresponding increase in time spent awake. In the SI group, the mean duration of sleep episodes decreased and delta activity during periods of wake increased. Control rats either lived in the treadmill without movement (cage controls, CC), or had 10-min periods of movement followed by 30 min of non-movement allowing deep/continuous sleep (exercise controls, EC). EC did not differ from baseline in the total time spent in each vigilance state. Hippocampal long-term potentiation (LTP), a long-lasting change in synaptic efficacy thought to underlie declarative memory formation, was absent in rats exposed to 24 and 72 h SI. In contrast, LTP was normal in EC rats. However, long-term depression and paired-pulse facilitation were unaltered by 24 h SI. Twenty-four hour SI also impaired acquisition of spatial learning in the hippocampus-dependent water maze test. Twenty-four hour SI elevated plasma corticosterone (CORT) to levels previously shown to enhance LTP (125 ng/mL). The results suggest that sleep fragmentation negatively impacts spatial learning. Loss of N-methyl-D-aspartate (NMDA) receptor-dependent LTP in the hippocampal CA1 region may be one mechanism involved in this deficit.
Tartar
Jaime L
JL
Harvard Medical School and VA Boston Healthcare System, Laboratory of Neuroscience, Research 151-C, 940 Belmont Street, Brockton, MA 02301, USA. jaime_tartar@hms.harvard.edu
Ward
Christopher P
CP
McKenna
James T
JT
Thakkar
Mahesh
M
Arrigoni
Elda
E
McCarley
Robert W
RW
Brown
Ritchie E
RE
Strecker
Robert E
RE
D000818:Animals; D003345:Corticosterone / Q000097:blood; D004569:Electroencephalography; D004576:Electromyography; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000502:physiology; D012892:Sleep Deprivation / Q000503:physiopathology*; D013037:Spatial Behavior / Q000502:physiology*
D003345:Corticosterone