title: Deleting both PHLPP1 and CANP1 rescues impairments in long-term potentiation and learning in both single knockout mice.
abstract: Calpain-1 (CANP1) has been shown to play a critical role in synaptic plasticity and learning and memory, as its deletion in mice results in impairment in theta-burst stimulation- (TBS) induced LTP and various forms of learning and memory. Likewise, PHLPP1 (aka SCOP) has also been found to participate in learning and memory, as PHLPP1 overexpression impairs hippocampus-dependent learning. We previously showed that TBS-induced LTP was associated with calpain-1 mediated truncation of PHLPP1.To better understand the roles of these 2 genes in synaptic plasticity and learning and memory, we generated a double knockout (DKO) mouse by crossing the parent strains. Surprisingly, DKO mice exhibit normal TBS-induced LTP, and the learning impairments in fear conditioning and novel object or novel location recognition were absent in the DKO mice. Moreover, TBS-induced ERK activation in field CA1 of hippocampal slices, which is impaired in both single deletion mice, was restored in the DKO mice. These results further strengthen the roles of both CANP1 and PHLPP1 in synaptic plasticity and learning and memory, and illustrate the complexities of the interactions between multiple pathways participating in synaptic plasticity.
authors.affiliation: Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, California 91766, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, California 91766, USA.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Sun
authors.affiliation: Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, California 91766, USA.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, California 91766, USA.
authors.forename: Dulce
authors.initials: D
authors.lastname: Lopez
authors.affiliation: Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, California 91766, USA College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, California 91766, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Tran
authors.affiliation: College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, California 91766, USA.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Bi
authors.affiliation: Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, California 91766, USA mbaudry@westernu.edu.
authors.forename: Michel
authors.initials: M
authors.lastname: Baudry
mesh_terms: D000818:Animals; D003214:Conditioning, Classical; D004558:Electric Stimulation; D005239:Fear; D006023:Glycoproteins / Q000235:genetics / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology; D007858:Learning / Q000502:physiology*; D017774:Long-Term Potentiation; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000502:physiology*; D065853:Spatial Learning / Q000502:physiology
chemical_list: D006023:Glycoproteins; D009687:Nuclear Proteins; C039304:calpain inhibitors; C519282:PHLPP1 protein, mouse; D010749:Phosphoprotein Phosphatases