Hepburn, Iain Jain, Anant Gangal, Himanshu Yamamoto, Yukio Tanaka-Yamamoto, Keiko De Schutter, Erik 2024-01-20T02:03:49Z 2024-01-20T02:03:49Z 2021-09-01 2017-02-06 1662-5099 https://pubs.kist.re.kr/handle/201004/123073 We report an updated stochastic model of cerebellar Long Term Depression (LTD) with improved realism. Firstly, we verify experimentally that dissociation of Raf kinase inhibitor protein (RKIP) from Mitogen-activated protein kinase kinase (MEK) is required for cerebellar LTD and add this interaction to an earlier published model, along with the known requirement of dissociation of RKIP from Raf kinase. We update Ca2+ dynamics as a constant-rate influx, which captures experimental input profiles accurately. We improve alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid (AMPA) receptor interactions by adding phosphorylation and dephosphorylation of AMPA receptors when bound to glutamate receptor interacting protein (GRIP). The updated model is tuned to reproduce experimental Ca2+ peak vs. LTD amplitude curves at four different Ca2+ pulse durations as closely as possible. We find that the updated model is generally more robust with these changes, yet we still observe some sensitivity of LTD induction to copy number of the key signaling molecule Protein kinase C (PKC). We predict natural variability in this number by stochastic diffusion may influence the probabilistic LTD response to Ca2+ input in Purkinje cell spines and propose this as an extra source of stochasticity that may be important also in other signaling systems. English FRONTIERS MEDIA SA KINASE INHIBITORY PROTEIN DENDRITIC SPINES SYNAPTIC DEPRESSION SIGNAL-TRANSDUCTION ACTIVATION PLASTICITY MECHANISM DIFFUSION PATHWAY ROLES A Model of Induction of Cerebellar Long-Term Depression Including RKIP Inactivation of Raf and MEK Article 10.3389/fnmol.2017.00019 1 FRONTIERS IN MOLECULAR NEUROSCIENCE, v.10 FRONTIERS IN MOLECULAR NEUROSCIENCE 10 scie scopus 000393285600001 2-s2.0-85014076127 Neurosciences Neurosciences & Neurology Article KINASE INHIBITORY PROTEIN DENDRITIC SPINES SYNAPTIC DEPRESSION SIGNAL-TRANSDUCTION ACTIVATION PLASTICITY MECHANISM DIFFUSION PATHWAY ROLES long-term depression Purkinje cell dendritic spine molecular modeling stochastic simulation cerebellum