Environmental enrichment enhances synaptic plasticity by internalization of striatal dopamine transporters

Well shit, this was written about in 2011 by Dr. Dale Corbett

enriched environment as talked about by Dr. Dale Corbett in 2011

How many times does the same information need to be repeated before our fucking failures of stroke associations take note and actually write up a stroke protocol on this. I bet the answer is that they never will do anything like this for survivors. Prove me wrong.

Environmental enrichment enhances synaptic plasticity by internalization of striatal dopamine transporters

1. Myung-Sun Kim1,2,*
2. Ji Hea Yu1,3,4,*
3. Chul Hoon Kim4,5,6
4. Jae Yong Choi5,7
5. Jung Hwa Seo1,4
6. Min-Young Lee1,2
7. Chi Hoon Yi8
8. Tae Hyun Choi8
9. Young Hoon Ryu7
10. Jong Eun Lee4,6,9
11. Bae Hwan Lee4,6,10
12. Hyongbum Kim5
13. Sung-Rae Cho1,2,4,11⇑

1. ¹Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Korea
2. ²Yonsei Stem Cell Center, Avison Biomedical Research Center, Seoul, Korea
3. ³Department of Medical Science, The Graduate School, Yonsei University, Seoul, Korea
4. ⁴Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Korea
5. ⁵Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea
6. ⁶Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea
7. ⁷Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, Korea
8. ⁸Department of Molecular Imaging, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
9. ⁹Department of Anatomy, Yonsei University College of Medicine, Seoul, Korea
10. ¹⁰Department of Physiology, Yonsei University College of Medicine, Seoul, Korea
11. ¹¹Rehabilitation Institute of Neuromuscular Disease, Yonsei University College of Medicine, Seoul, Korea

1. Sung-Rae Cho, Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea. Email: srcho918@yuhs.ac

1. ↵* These authors contributed equally to this work

Abstract

Environmental enrichment (EE) with a complex combination of physical, cognitive and social stimulations enhances synaptic plasticity and behavioral function. However, the mechanism remains to be elucidated in detail. We aimed to investigate dopamine-related synaptic plasticity underlying functional improvement after EE. For this, six-week-old CD-1 mice were randomly allocated to EE or standard conditions for two months. EE significantly enhanced behavioral functions such as rotarod and ladder walking tests. In a [¹⁸F]FPCIT positron emission tomography scan, binding values of striatal DAT were significantly decreased approximately 18% in the EE mice relative to the control mice. DAT inhibitor administrated to establish the relationship of the DAT down-regulation to the treatment effects also improved rotarod performances, suggesting that DAT inhibition recapitulated EE-mediated treatment benefits. Next, EE-induced internalization of DAT was confirmed using a surface biotinylation assay. In situ proximity ligation assay and immunoprecipitation demonstrated that EE significantly increased the phosphorylation of striatal DAT as well as the levels of DAT bound with protein kinase C (PKC). In conclusion, we suggest that EE enables phosphorylation of striatal DAT via a PKC-mediated pathway and causes DAT internalization. This is the first report to suggest an EE-mediated mechanism of synaptic plasticity by internalization of striatal DAT.