title: Pathological α-synuclein impairs adult-born granule cell development and functional integration in the olfactory bulb.
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.
authors.affiliation: Center for Neuropathology and Prion Research, Department for Translationsal Brain Research, Ludwig Maximilian University, Feodor-Lynen-Strassee 23, Munich 81377, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Neuner
authors.affiliation: German Center for Neurodegeneratione Diseases (DZNE), Department for Translational Brain Research, Feodor-Lynen-Strasse 23, Munich 81377, Germany.
authors.forename: Saak V
authors.initials: SV
authors.lastname: Ovsepian
authors.affiliation: Center for Neuropathology and Prion Research, Department for Translationsal Brain Research, Ludwig Maximilian University, Feodor-Lynen-Strassee 23, Munich 81377, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Dorostkar
authors.affiliation: German Center for Neurodegeneratione Diseases (DZNE), Department for Translational Brain Research, Feodor-Lynen-Strasse 23, Munich 81377, Germany.
authors.forename: Severin
authors.initials: S
authors.lastname: Filser
authors.affiliation: Center for Neuropathology and Prion Research, Department for Translationsal Brain Research, Ludwig Maximilian University, Feodor-Lynen-Strassee 23, Munich 81377, Germany.
authors.forename: Aayush
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Center for Integrated Protein Science Munich, (CiPSM) and Department of Pharmacy-Center for Drug Research, Ludwig Maximilian University, Butenandtstrasse 5-13, Munich 81377, Germany.
authors.forename: Stylianos
authors.initials: S
authors.lastname: Michalakis
authors.affiliation: Center for Integrated Protein Science Munich, (CiPSM) and Department of Pharmacy-Center for Drug Research, Ludwig Maximilian University, Butenandtstrasse 5-13, Munich 81377, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Biel
authors.affiliation: 1] German Center for Neurodegeneratione Diseases (DZNE), Department for Translational Brain Research, Feodor-Lynen-Strasse 23, Munich 81377, Germany [2] Munich Cluster of Systems Neurology (SyNergy), Ludwig Maximilian University, Feodor-Lynen-Strasse 23, Munich 81377, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Herms
mesh_terms: D000375:Aging; D000818:Animals; D049229:Dendritic Spines / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials; D059330:GABAergic Neurons / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D050505:Mutant Proteins / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology* / Q000378:metabolism*; D016019:Survival Analysis; D013569:Synapses / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D050505:Mutant Proteins; C497605:Snca protein, mouse; D051844:alpha-Synuclein