STIM1 Controls Neuronal Ca2+ Signaling, mGluR1-Dependent Synaptic Transmission, and Cerebellar Motor Behavior

• Published in: Neuron (Cambridge, Mass.) Mass.), 2014-05, Vol.82 (3), p.635-644
• Main Authors: Hartmann, Jana, Karl, Rosa M., Alexander, Ryan P.D., Adelsberger, Helmuth, Brill, Monika S., Rühlmann, Charlotta, Ansel, Anna, Sakimura, Kenji, Baba, Yoshihiro, Kurosaki, Tomohiro, Misgeld, Thomas, Konnerth, Arthur
• Format: Article
• Language: English
• Subjects: Animals; Ataxia; Behavior; Brain research; Calcium Channels; Calcium Signaling - physiology; Cerebellum - cytology; Cerebellum - physiology; Excitatory Postsynaptic Potentials - physiology; Mammals; Membrane Glycoproteins - physiology; Mice; Mice, Knockout; Mice, Transgenic; Motor Activity - physiology; Neurons; Neurons - physiology; Organ Culture Techniques; Receptors, Metabotropic Glutamate - physiology; Stromal Interaction Molecule 1; Synaptic Transmission - physiology
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2014.03.027

In central mammalian neurons, activation of metabotropic glutamate receptor type1 (mGluR1) evokes a complex synaptic response consisting of IP3 receptor-dependent Ca2+ release from internal Ca2+ stores and a slow depolarizing potential involving TRPC3 channels. It is largely unclear how mGluR1 is linked to its downstream effectors. Here, we explored the role of stromal interaction molecule 1 (STIM1) in regulating neuronal Ca2+ signaling and mGluR1-dependent synaptic transmission. By analyzing mouse cerebellar Purkinje neurons, we demonstrate that STIM1 is an essential regulator of the Ca2+ level in neuronal endoplasmic reticulum Ca2+ stores. Both mGluR1-dependent synaptic potentials and IP3 receptor-dependent Ca2+ signals are strongly attenuated in the absence of STIM1. Furthermore, the Purkinje neuron-specific deletion of Stim1 causes impairments in cerebellar motor behavior. Together, our results demonstrate that in the mammalian nervous system STIM1 is a key regulator of intracellular Ca2+ signaling, metabotropic glutamate receptor-dependent synaptic transmission, and motor coordination. •STIM1 is strongly expressed in cerebellar Purkinje neurons•STIM1 controls endoplasmic reticulum Ca2+ stores in Purkinje neurons•STIM1 regulates mGluR1/TRPC3-dependent slow excitatory synaptic potentials•Selective deletion of STIM1 in Purkinje neurons impairs cerebellar motor behavior By analyzing cerebellar Purkinje neuron-specific mouse mutants, Hartmann et al. demonstrate that STIM1 is a key regulator of intracellular neuronal calcium signaling that determines metabotropic glutamate receptor-dependent synaptic transmission and cerebellar motor behavior.