Figure 6
From: Modeled changes of cerebellar activity in mutant mice are predictive of their learning impairments
The model can reproduce neither behavioral nor electrophysiological changes during VOR phase-reversal in PC-ΔPP2B mice.
(a) Simplified view of molecular pathways involved in PF to PC plasticity and role of protein phosphatase 2B (PP2B, orange frame). LTD is induced by simultaneous CF and PF activation (purple and green). A large Ca2+ transient resulting from Ca2+ influx together with release of Ca2+ from intracellular stores mediated by IP3, promotes protein kinase C (PKC) activation, which phosphorylates AMPA receptors leading to their internalization. PF activation also causes presynaptic release of nitric oxide (NO) and results in activation of protein kinase G (PKG), which inhibits PP2B and thus inhibits dephosphorylation of AMPA receptors. Stimulation of PFs alone leads to a much smaller Ca2+ influx, promoting activation of PP2B and regulating AMPA receptor insertion leading to LTP. (b) Experimental and modeled eye movements in PC-ΔPP2B mice as a function of training time of VOR phase-reversal training. Gain values (top panel) are normalized to the initial gain. Experimental data represent averages with SEM (orange shaded area) and SD (grey shaded area) of the PC-ΔPP2B mice. Grey dotted line indicates the values of the littermate controls. Note that the modeled values (red) are locked at the gain of 1 and phase of 0 due to the blockage of the potentiation at the PF-PC synapse. (c) Representative PSTHs from in vivo recording in PC-ΔPP2B during vestibular stimulation (0.6 Hz). (d) Polar plots of SS and CS modulation before and after learning (lighter and darker orange, respectively). Note that some PCs did not modulate their SS activity (indicated with black arrows). Each dot represents a single cell. Phase of the modeled SS and CS are indicated with the arrows. (e) Our model predicted low modulation of the SS modulation but failed to reproduce initial and trained firing frequencies. Error bars denote SD; *denote p < 0.05; **denote p < 0.001. (f) PC SS activity as a function of time in the cycle in a model with no PF-PC LTP. Note that the model cannot reproduce the experimental data due to the limitations explained in the discussion and methods.
