Advanced

Striatonigral neurons divide into two distinct morphological-physiological phenotypes after chronic L-DOPA treatment in parkinsonian rats

Fieblinger, T. LU ; Zanetti, L. LU ; Sebastianutto, I. LU ; Breger, L. S. LU ; Quintino, L. LU ; Lockowandt, M. LU ; Lundberg, C. LU and Cenci, M. A. LU (2018) In Scientific Reports 8(1).
Abstract

Dendritic regression of striatal spiny projection neurons (SPNs) is a pathological hallmark of Parkinson's disease (PD). Here we investigate how chronic dopamine denervation and dopamine replacement with L-DOPA affect the morphology and physiology of direct pathway SPNs (dSPNS) in the rat striatum. We used a lentiviral vector optimized for retrograde labeling (FuG-B-GFP) to identify dSPNs in rats with 6-hydroxydopamine (6-OHDA) lesions. Changes in morphology and physiology of dSPNs were assessed through a combination of patch-clamp recordings and two photon microscopy. The 6-OHDA lesion caused a significant reduction in dSPN dendritic complexity. Following chronic L-DOPA treatment, dSPNs segregated into two equal-sized clusters. One... (More)

Dendritic regression of striatal spiny projection neurons (SPNs) is a pathological hallmark of Parkinson's disease (PD). Here we investigate how chronic dopamine denervation and dopamine replacement with L-DOPA affect the morphology and physiology of direct pathway SPNs (dSPNS) in the rat striatum. We used a lentiviral vector optimized for retrograde labeling (FuG-B-GFP) to identify dSPNs in rats with 6-hydroxydopamine (6-OHDA) lesions. Changes in morphology and physiology of dSPNs were assessed through a combination of patch-clamp recordings and two photon microscopy. The 6-OHDA lesion caused a significant reduction in dSPN dendritic complexity. Following chronic L-DOPA treatment, dSPNs segregated into two equal-sized clusters. One group (here called "cluster-1"), showed sustained dendritic atrophy and a partially normalized electrophysiological phenotype. The other one ("cluster-2") exhibited dendritic regrowth and a strong reduction of intrinsic excitability. Interestingly, FosB/ΔFosB induction by L-DOPA treatment occurred preferentially in cluster-2 dSPNs. Our study demonstrates the feasibility of retrograde FuG-B-GFP labeling to study dSPNs in the rat and reveals, for the first time, that a subgroup of dSPNs shows dendritic sprouting in response to chronic L-DOPA treatment. Investigating the mechanisms and significance of this response will greatly improve our understanding of the adaptations induced by dopamine replacement therapy in PD.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
8
issue
1
publisher
Nature Publishing Group
external identifiers
  • scopus:85049515538
ISSN
2045-2322
DOI
10.1038/s41598-018-28273-5
language
English
LU publication?
yes
id
2584d680-afbf-450e-a083-774b8b4bde19
date added to LUP
2018-07-20 08:50:53
date last changed
2019-04-21 05:15:47
@article{2584d680-afbf-450e-a083-774b8b4bde19,
  abstract     = {<p>Dendritic regression of striatal spiny projection neurons (SPNs) is a pathological hallmark of Parkinson's disease (PD). Here we investigate how chronic dopamine denervation and dopamine replacement with L-DOPA affect the morphology and physiology of direct pathway SPNs (dSPNS) in the rat striatum. We used a lentiviral vector optimized for retrograde labeling (FuG-B-GFP) to identify dSPNs in rats with 6-hydroxydopamine (6-OHDA) lesions. Changes in morphology and physiology of dSPNs were assessed through a combination of patch-clamp recordings and two photon microscopy. The 6-OHDA lesion caused a significant reduction in dSPN dendritic complexity. Following chronic L-DOPA treatment, dSPNs segregated into two equal-sized clusters. One group (here called "cluster-1"), showed sustained dendritic atrophy and a partially normalized electrophysiological phenotype. The other one ("cluster-2") exhibited dendritic regrowth and a strong reduction of intrinsic excitability. Interestingly, FosB/ΔFosB induction by L-DOPA treatment occurred preferentially in cluster-2 dSPNs. Our study demonstrates the feasibility of retrograde FuG-B-GFP labeling to study dSPNs in the rat and reveals, for the first time, that a subgroup of dSPNs shows dendritic sprouting in response to chronic L-DOPA treatment. Investigating the mechanisms and significance of this response will greatly improve our understanding of the adaptations induced by dopamine replacement therapy in PD.</p>},
  articleno    = {10068},
  author       = {Fieblinger, T. and Zanetti, L. and Sebastianutto, I. and Breger, L. S. and Quintino, L. and Lockowandt, M. and Lundberg, C. and Cenci, M. A.},
  issn         = {2045-2322},
  language     = {eng},
  month        = {12},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Striatonigral neurons divide into two distinct morphological-physiological phenotypes after chronic L-DOPA treatment in parkinsonian rats},
  url          = {http://dx.doi.org/10.1038/s41598-018-28273-5},
  volume       = {8},
  year         = {2018},
}