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Pathological α-synuclein impairs adult-born granule cell development and functional integration in the olfactory bulb

Author

Listed:
  • Johanna Neuner

    (Center for Neuropathology and Prion Research, Ludwig Maximilian University)

  • Saak V. Ovsepian

    (German Center for Neurodegeneratione Diseases (DZNE))

  • Mario Dorostkar

    (Center for Neuropathology and Prion Research, Ludwig Maximilian University)

  • Severin Filser

    (German Center for Neurodegeneratione Diseases (DZNE))

  • Aayush Gupta

    (Center for Neuropathology and Prion Research, Ludwig Maximilian University)

  • Stylianos Michalakis

    (Center for Integrated Protein Science Munich, Ludwig Maximilian University)

  • Martin Biel

    (Center for Integrated Protein Science Munich, Ludwig Maximilian University)

  • Jochen Herms

    (German Center for Neurodegeneratione Diseases (DZNE)
    Munich Cluster of Systems Neurology (SyNergy), Ludwig Maximilian University)

Abstract

Although the role of noxious α-synuclein (α-SYN) in the degeneration of midbrain dopaminergic neurons and associated motor deficits of Parkinson’s disease is recognized, its impact on non-motor brain circuits and related symptoms remains elusive. Through combining in vivo two-photon imaging with time-coded labelling of neurons in the olfactory bulb of A30P α-SYN transgenic mice, we show impaired growth and branching of dendrites of adult-born granule cells (GCs), with reduced gain and plasticity of dendritic spines. The spine impairments are especially pronounced during the critical phase of integration of new neurons into existing circuits. Functionally, retarded dendritic expansion translates into reduced electrical capacitance with enhanced intrinsic excitability and responsiveness of GCs to depolarizing inputs, while the spine loss correlates with decreased frequency of AMPA-mediated miniature EPSCs. Changes described here are expected to interfere with the functional integration and survival of new GCs into bulbar networks, contributing towards olfactory deficits and related behavioural impairments.

Suggested Citation

  • Johanna Neuner & Saak V. Ovsepian & Mario Dorostkar & Severin Filser & Aayush Gupta & Stylianos Michalakis & Martin Biel & Jochen Herms, 2014. "Pathological α-synuclein impairs adult-born granule cell development and functional integration in the olfactory bulb," Nature Communications, Nature, vol. 5(1), pages 1-12, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4915
    DOI: 10.1038/ncomms4915
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