The stromal interaction molecule 1 (STIM1) is an ER-Ca21 sensor and an essential component of ER-Ca21 store operated Ca21 entry. Loss of STIM1 affects metabotropic glutamate receptor 1 (mGluR1)-mediated synaptic transmission, neuronal Ca21 homeostasis, and intrinsic plasticity in Purkinje neurons (PNs). Long-term changes of intracellular Ca21 signaling in PNs led to neurodegenerative conditions, as evident in individuals with mutations of the ER-Ca21 channel, the inositol 1,4,5- triphosphate receptor. Here, we asked whether changes in such intrinsic neuronal properties, because of loss of STIM1, have an age-dependent impact on PNs. Consequently, we analyzed mRNA expression profiles and cerebellar morphology in PNspecific STIM1 KO mice (STIM1PKO) of both sexes across ages. Our study identified a requirement for STIM1-mediated Ca21 signaling in maintaining the expression of genes belonging to key biological networks of synaptic function and neurite development among others. Gene expression changes correlated with altered patterns of dendritic morphology and greater innervation of PN dendrites by climbing fibers, in aging STIM1PKO mice. Together, our data identify STIM1 as an important regulator of Ca21 homeostasis and neuronal excitability in turn required for maintaining the optimal transcriptional profile of PNs with age. Our findings are significant in the context of understanding how dysregulated calcium signals impact cellular mechanisms in multiple neurodegenerative disorders.
CITATION STYLE
Dhanya, S. K., & Hasan, G. (2021). Purkinje neurons with loss of stim1 exhibit age-dependent changes in gene expression and synaptic components. Journal of Neuroscience, 41(17), 3777–3798. https://doi.org/10.1523/JNEUROSCI.2401-20.2021
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