title: Occlusion of low-frequency-induced, heterosynaptic long-term potentiation in the rat hippocampus in vivo following spatial training.
abstract: Recent work has shown that some low-frequency stimulation (LFS) protocols can induce long-term potentiation (LTP) at hippocampal synapses. As LFS mimics certain aspects of low-frequency oscillations during slow-wave sleep, LFS-LTP may be relevant to processes of sleep-dependent consolidation. Here, alternating LFS (1 Hz) of heterosynaptic inputs arising in the medial septum and area CA3 induced LTP at hippocampal CA1 synapses of anesthetized rats. Remarkably, this LTP was absent when delivered 3 h, but not 8 or 24 h, after training in the hidden platform version of the Morris water maze, suggesting a time-specific occlusion of LFS-LTP following spatial learning. LTP assessed 3 h after training was intact in yoked swim controls and rats trained in darkness. Visible platform training resulted in heterogeneous effects, with about half of the animals showing LTP occlusion. Pharmacological experiments revealed that N-methyl-d-aspartate (NMDA)-receptor activation was required for both LFS-LTP and the retention of spatial learning. To test whether a learning-related, NMDA-dependent potentiation accounted for the occlusion effect, we blocked NMDA receptors immediately following spatial training. This manipulation reversed LTP occlusion 3 h after training. Together, these experiments indicate a mechanistic overlap between heterosynaptically induced LFS-LTP and processes mediating the consolidation of spatial information at hippocampal synapses.
authors.affiliation: Centre for Neuroscience Studies and.
authors.forename: Diala
authors.initials: D
authors.lastname: Habib
authors.affiliation: Department of Psychology, Queen's University, Kingston, Ontario, Canada K7L 3N6.
authors.forename: Claudia K Y
authors.initials: CK
authors.lastname: Tsui
authors.affiliation: Centre for Neuroscience Studies and.
authors.forename: Laura G
authors.initials: LG
authors.lastname: Rosen
authors.affiliation: Centre for Neuroscience Studies and Department of Psychology, Queen's University, Kingston, Ontario, Canada K7L 3N6.
authors.forename: Hans C
authors.initials: HC
authors.lastname: Dringenberg
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D055592:Biophysical Phenomena / Q000502:physiology*; D001703:Biophysics; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects; D013028:Space Perception / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects; D013997:Time Factors
chemical_list: D018691:Excitatory Amino Acid Antagonists; D010879:Piperazines; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid
keywords: hippocampus; learning; low-frequency LTP; sleep