title: Hippocampal metaplasticity is required for the formation of temporal associative memories.
abstract: Metaplasticity regulates the threshold for modification of synaptic strength and is an important regulator of learning rules; however, it is not known whether these cellular mechanisms for homeostatic regulation of synapses contribute to particular forms of learning. Conditional ablation of mGluR5 in CA1 pyramidal neurons resulted in the inability of low-frequency trains of afferent activation to prime synapses for subsequent theta burst potentiation. Priming-induced metaplasticity requires mGluR5-mediated mobilization of endocannabinoids during the priming train to induce long-term depression of inhibition (I-LTD). Mice lacking priming-induced plasticity had no deficit in spatial reference memory tasks, but were impaired in an associative task with a temporal component. Conversely, enhancing endocannabinoid signaling facilitated temporal associative memory acquisition and, after training animals in these tasks, ex vivo I-LTD was partially occluded and theta burst LTP was enhanced. Together, these results suggest a link between metaplasticity mechanisms in the hippocampus and the formation of temporal associative memories.
authors.affiliation: Department of Physiology, Northwestern University Feinberg School of Medicine, and.
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Physiology, Northwestern University Feinberg School of Medicine, and.
authors.forename: Marcia D
authors.initials: MD
authors.lastname: Antion
authors.affiliation: Department of Physiology, Northwestern University Feinberg School of Medicine, and.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nomura
authors.affiliation: Department of Physiology, Northwestern University Feinberg School of Medicine, and.
authors.forename: Stephen
authors.initials: S
authors.lastname: Kraniotis
authors.affiliation: Department of Physiology, Northwestern University Feinberg School of Medicine, and.
authors.forename: Yongling
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Physiology, Northwestern University Feinberg School of Medicine, and Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Chicago, Illinois 60611 a-contractor@northwestern.edu.
authors.forename: Anis
authors.identifier: http://orcid.org/0000-0002-5131-2536
authors.initials: A
authors.lastname: Contractor
mesh_terms: D000818:Animals; D001245:Association Learning / Q000502:physiology*; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D005260:Female; D017774:Long-Term Potentiation / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology*; D009924:Organ Culture Techniques; D064529:Receptor, Metabotropic Glutamate 5 / Q000502:physiology*; D013997:Time Factors
chemical_list: C578936:Grm5 protein, mouse; D064529:Receptor, Metabotropic Glutamate 5
keywords: endocannabinoid; mGluR5; memory; metaplasticity