Modelling bidirectional modulations in synaptic plasticity: A biochemical pathway model to understand the emergence of long term potentiation (LTP) and long term depression (LTD). (21st August 2016)

• Record Type: Journal Article
• Authors: He, Yao; Kulasiri, Don; Samarasinghe, Sandhya
• Is Part Of: Journal of theoretical biology. Volume 403(2016)
• Page Start: 159
• Page End: 177
• Publication Date: 2016-08-21
• Subjects: AC adenylyl cyclase -- AMPAR a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor -- AMP adenosine monophosphate -- ATP adenosine triphosphate -- CaM calmodulin -- CaMKII calcium/calmodulin-dependent protein kinase II -- cAMP cyclic adenosine monophosphate -- CaNA calcineurin A subunit of PP2B -- I1 inhibitor 1 -- EPSC excitatory postsynaptic current -- EPSP excitatory postsynaptic potential -- HFS high frequency stimulations -- LFS low frequency stimulations -- LHS Latin hypercube sampling -- LTP long-term potentiation -- LTD long-term depression -- NMDAR N-methyl-D-aspartate receptor -- PDE phosphodiesterase -- PKA protein kinase A/cyclic AMP-dependent protein kinase -- PP1 protein phosphatase 1 -- PP2A protein phosphatase 2a -- PP2B protein phosphatase 2b, calcineurin -- PSD postsynaptic density -- S831 serine 831 residue of AMPAR -- S845 serine 845 residue of AMPAR -- TBS theta burst stimulation; Bidirectional modulation -- Long term potentiation (LTP) -- Long term depression (LTD) -- Synaptic plasticity -- Modelling -- Biochemical pathways; Biology -- Periodicals; Biological Science Disciplines -- Periodicals; Biology -- Periodicals; Biologie -- Périodiques; Theoretische biologie; Biology; Periodicals; 571.05
• DOI: 10.1016/j.jtbi.2016.05.015
• Languages: English
• ISSNs: 0022-5193

Abstract

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. Highlights: Development of a simplified integrated model of the emergence of synaptic plasticity. The model explains Ca 2+ /calmodulin complex dependent coordination of LTP/LTD expressions. A decline in calmodulin pool size can contribute to cognitive impairment during aging.