title: Modelling bidirectional modulations in synaptic plasticity: A biochemical pathway model to understand the emergence of long term potentiation (LTP) and long term depression (LTD).
abstract: Synaptic plasticity induces bidirectional modulations of the postsynaptic response following a synaptic transmission. The long term forms of synaptic plasticity, named long term potentiation (LTP) and long term depression (LTD), are critical for the antithetic functions of the memory system, memory formation and removal, respectively. A common Ca(2+) signalling upstream triggers both LTP and LTD, and the critical proteins and factors coordinating the LTP/LTD inductions are not well understood. We develop an integrated model based on the sub-models of the indispensable synaptic proteins in the emergence of synaptic plasticity to validate and understand their potential roles in the expression of synaptic plasticity. The model explains Ca(2+)/calmodulin (CaM) complex dependent coordination of LTP/LTD expressions by the interactions among the indispensable proteins using the experimentally estimated kinetic parameters. Analysis of the integrated model provides us with insights into the effective timescales of the key proteins and we conclude that the CaM pool size is critical for the coordination between LTP/LTD expressions.
authors.affiliation: Centre for Advanced Computational Solutions (C-fACS), Molecular Biosciences Department, Lincoln University, Christchurch, New Zealand.
authors.forename: Yao
authors.initials: Y
authors.lastname: He
authors.affiliation: Centre for Advanced Computational Solutions (C-fACS), Molecular Biosciences Department, Lincoln University, Christchurch, New Zealand. Electronic address: don.kulasiri@lincoln.ac.nz.
authors.forename: Don
authors.initials: D
authors.lastname: Kulasiri
authors.affiliation: Centre for Advanced Computational Solutions (C-fACS), Molecular Biosciences Department, Lincoln University, Christchurch, New Zealand.
authors.forename: Sandhya
authors.initials: S
authors.lastname: Samarasinghe
mesh_terms: D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D008959:Models, Neurological; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D019703:Calcineurin; D002118:Calcium
keywords: Bidirectional modulation; Biochemical pathways; Long term depression (LTD); Long term potentiation (LTP); Modelling; Synaptic plasticity