title: Impaired learning in mice with abnormal short-lived plasticity.
abstract: BACKGROUND
  Many studies suggest that long term potentiation (LTP) has a role in learning and memory. In contrast, little is known about the function of short-lived plasticity (SLP). Modeling results suggested that SLP could be responsible for temporary memory storage, as in working memory, or that it may be involved in processing information regarding the timing of events. These models predict that abnormalities in SLP should lead to learning deficits. We tested this prediction in four lines of mutant mice with abnormal SLP, but apparently normal LTP-mice heterozygous for a alpha-calcium calmodulin kinase II mutation (alpha CaMKII +/-) have lower paired-pulse facilitation (PPF) and increased post-tetanic potentiation (PTP); mice lacking synapsin II (SyII-/-), and mice defective in both synapsin I and synapsin II (SyI/II-/-), show normal PPF but lower PTP; in contrast, mice just lacking synapsin I (SyI-/-) have increased PPF, but normal PTP.
  
  
  RESULTS
  Our behavioral results demonstrate that alpha CaMKII +/-, SyII-/- and SyI/II-/- mutant mice, which have decreased PPF or PTP, have profound impairments in learning tasks. In contrast, behavioral analysis did not reveal learning deficits in SyI-/- mice, which have increased PPF.
  
  
  CONCLUSIONS
  Our results are consistent with models that propose a role for SLP in learning, as mice with decreased PPF or PTP, in the absence of known LTP deficits, also show profound learning impairments. Importantly, analysis of the SyI-/- mutants demonstrated that an increase in PPF does not disrupt learning.
authors.affiliation: Cold Spring Harbor Laboratory, New York 11724, USA. Silva@CSHL.ORG
authors.forename: A J
authors.initials: AJ
authors.lastname: Silva
authors.forename: T W
authors.initials: TW
authors.lastname: Rosahl
authors.forename: P F
authors.initials: PF
authors.lastname: Chapman
authors.forename: Z
authors.initials: Z
authors.lastname: Marowitz
authors.forename: E
authors.initials: E
authors.lastname: Friedman
authors.forename: P W
authors.initials: PW
authors.lastname: Frankland
authors.forename: V
authors.initials: V
authors.lastname: Cestari
authors.forename: D
authors.initials: D
authors.lastname: Cioffi
authors.forename: T C
authors.initials: TC
authors.lastname: Südhof
authors.forename: R
authors.initials: R
authors.lastname: Bourtchuladze
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D007858:Learning / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000502:physiology*; D016704:Synapsins / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission
chemical_list: D016704:Synapsins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases