Striatonigral neurons divide into two distinct morphological-physiological phenotypes after chronic L-DOPA treatment in parkinsonian rats
(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)
- author
- 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
- organization
- publishing date
- 2018-12-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scientific Reports
- volume
- 8
- issue
- 1
- article number
- 10068
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85049515538
- pmid:29968767
- 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
- 2024-09-17 00:22:48
@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>}}, 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}}, doi = {{10.1038/s41598-018-28273-5}}, volume = {{8}}, year = {{2018}}, }