title: A distinct subtype of dopaminergic interneuron displays inverted structural plasticity at the axon initial segment.
abstract: The axon initial segment (AIS) is a specialized structure near the start of the axon that is a site of neuronal plasticity. Changes in activity levels in vitro and in vivo can produce structural AIS changes in excitatory cells that have been linked to alterations in excitability, but these effects have never been described in inhibitory interneurons. In the mammalian olfactory bulb (OB), dopaminergic interneurons are particularly plastic, undergoing constitutive turnover throughout life and regulating tyrosine hydroxylase expression in an activity-dependent manner. Here we used dissociated cultures of rat and mouse OB to show that a subset of bulbar dopaminergic neurons possess an AIS and that these AIS-positive cells are morphologically and functionally distinct from their AIS-negative counterparts. Under baseline conditions, OB dopaminergic AISs were short and located distally along the axon but, in response to chronic 24 h depolarization, lengthened and relocated proximally toward the soma. These activity-dependent changes were in the opposite direction to both those we saw in non-GABAergic OB neurons and those reported previously for excitatory cell types. Inverted AIS plasticity in OB dopaminergic cells was bidirectional, involved all major components of the structure, was dependent on the activity of L-type CaV1 calcium channels but not on the activity of the calcium-activated phosphatase calcineurin, and was opposed by the actions of cyclin-dependent kinase 5. Such distinct forms of AIS plasticity in inhibitory interneurons and excitatory projection neurons may allow considerable flexibility when neuronal networks must adapt to perturbations in their ongoing activity.
authors: Medical Research Council Centre for Developmental Neurobiology, King's College London, London SE1 1UL, United Kingdom.
authors: Annisa N
authors: http://orcid.org/0000-0002-0178-1094
authors: AN
authors: Chand
authors: Medical Research Council Centre for Developmental Neurobiology, King's College London, London SE1 1UL, United Kingdom.
authors: Elisa
authors: http://orcid.org/0000-0002-6941-766X
authors: E
authors: Galliano
authors: Medical Research Council Centre for Developmental Neurobiology, King's College London, London SE1 1UL, United Kingdom.
authors: Robert A
authors: RA
authors: Chesters
authors: Medical Research Council Centre for Developmental Neurobiology, King's College London, London SE1 1UL, United Kingdom matthew.grubb@kcl.ac.uk.
authors: Matthew S
authors: http://orcid.org/0000-0002-2673-274X
authors: MS
authors: Grubb
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000145:classification* / Q000187:drug effects / Q000502:physiology*; D004622:Embryo, Mammalian; D005260:Female; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
chemical_list: D008164:Luminescent Proteins; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D014446:Tyrosine 3-Monooxygenase; D051360:Cyclin-Dependent Kinase 5
keywords: axon initial segment; dopamine; interneuron; olfactory bulb; plasticity
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