title: Impairment in long-term memory formation and learning-dependent synaptic plasticity in mice lacking glycogen synthase in the brain.
abstract: Glycogen is the only carbohydrate reserve of the brain, but its overall contribution to brain functions remains unclear. Although it has traditionally been considered as an emergency energetic reservoir, increasing evidence points to a role of glycogen in the normal activity of the brain. To address this long-standing question, we generated a brain-specific Glycogen Synthase knockout (GYS1(Nestin-KO)) mouse and studied the functional consequences of the lack of glycogen in the brain under alert behaving conditions. These animals showed a significant deficiency in the acquisition of an associative learning task and in the concomitant activity-dependent changes in hippocampal synaptic strength. Long-term potentiation (LTP) evoked in the hippocampal CA3-CA1 synapse was also decreased in behaving GYS1(Nestin-KO) mice. These results unequivocally show a key role of brain glycogen in the proper acquisition of new motor and cognitive abilities and in the underlying changes in synaptic strength.
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona) Barcelona, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Duran
authors.forename: Isabel
authors.initials: I
authors.lastname: Saez
authors.forename: Agnès
authors.initials: A
authors.lastname: Gruart
authors.forename: Joan J
authors.initials: JJ
authors.lastname: Guinovart
authors.forename: José M
authors.initials: JM
authors.lastname: Delgado-García
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000201:enzymology*; D056654:CA3 Region, Hippocampal / Q000166:cytology / Q000201:enzymology*; D003071:Cognition / Q000502:physiology; D006003:Glycogen / Q000235:genetics / Q000378:metabolism*; D006006:Glycogen Synthase / Q000235:genetics / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000502:physiology; D057567:Memory, Long-Term / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000235:genetics / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D006003:Glycogen; D006006:Glycogen Synthase