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Cerebellar Epigenetics: Transcription of microRNAs in Purkinje Neurons as an Approach to Neuronal Plasticity

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Essentials of Cerebellum and Cerebellar Disorders

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Abstract

Cerebellar plasticity is often investigated using brief electrical coactivation of climbing and parallel fiber pathways to evoke Long Term Depression (LTD), a temporary decrease in the excitability of Purkinje cell Simple Spikes (SSs). The mechanistic importance of individual proteins in climbing fiber-evoked depression of simple spikes can be approached by examining the longer-term role of regulated microRNA transcription. In this review, we examine the consequences of longer activation (1–30 h) of climbing fibers on the expression of microRNAs, mRNAs and proteins in targeted Purkinje cells of the mouse. Horizontal optokinetic stimulation (HOKS) of unanesthetized mice increases climbing fiber discharge of floccular Purkinje cells ipsilateral to the stimulated eye. This increased climbing fiber discharge increases the expression of several microRNA and mRNA transcripts. One of these transcripts, miR335, increases 18X after 24 h of HOKS. Pri-miR335 transcripts increase 28X after 24 h of HOKS. miR335 transcripts decay with a time constant of ~2.5 h. Increases in miR335 transcripts are coupled with decreases in the expression of calbindin, 14-3-3-θ and protein kinase C-γ (PKC-ɣ). This interaction is critical for the serine phosphorylation of the GABAA-ɣ2 receptor and its membrane expression in Purkinje cells and may contribute to homeostatic regulation of Purkinje cell discharge of SSs.

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, OR, USA

    Neal H. Barmack

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  1. Neal H. Barmack
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Correspondence to Neal H. Barmack .

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Editors and Affiliations

  1. Neuroscience Department, The Scripps Research Institute, La Jolla, CA, USA

    Donna L. Gruol

  2. Department of Integrative Physiology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan

    Noriyuki Koibuchi

  3. Service de Neurologie, CHU-Charleroi, Charleroi, Belgium

    Mario Manto

  4. Clinical Translational Research, Santa Lucia Foundation, Rome, Italy

    Marco Molinari

  5. Ataxia Center, Cognitive Behavioral Neurology Unit, Laboratory for Neuroanatomy and Cerebellar Neurobiology, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Jeremy D. Schmahmann

  6. Department of Physiology, Zhejiang University School of Medicine, Hangzho, China

    Ying Shen

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Barmack, N.H. (2023). Cerebellar Epigenetics: Transcription of microRNAs in Purkinje Neurons as an Approach to Neuronal Plasticity. In: Gruol, D.L., Koibuchi, N., Manto, M., Molinari, M., Schmahmann, J.D., Shen, Y. (eds) Essentials of Cerebellum and Cerebellar Disorders. Springer, Cham. https://doi.org/10.1007/978-3-031-15070-8_19

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