Abstract
Compelling evidence demonstrates that the external globus pallidus (GPe) plays a key role in processing sensorimotor information. An anatomical projection from the GPe to the dorsal striatum has been described for decades. However, the cellular target and functional impact of this projection remain unknown. Using cell-specific transgenic mice, modern monosynaptic tracing techniques, and optogenetics-based mapping, we discovered that GPe neurons provide inhibitory inputs to direct and indirect pathway striatal projection neurons (SPNs). Our results indicate that the GPe input to SPNs arises primarily from Npas1-expressing neurons and is strengthened in a chronic Parkinson's disease (PD) model. Alterations of the GPe-SPN input in a PD model argue for the critical position of this connection in regulating basal ganglia motor output and PD symptomatology. Finally, chemogenetic activation of Npas1-expressing GPe neurons suppresses motor output, arguing that strengthening of the GPe-SPN connection is maladaptive and may underlie the hypokinetic symptoms in PD.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 5472-5488 |
| Number of pages | 17 |
| Journal | Journal of Neuroscience |
| Volume | 36 |
| Issue number | 20 |
| DOIs | |
| State | Published - May 18 2016 |
Funding
This work was supported by grants from the Parkinson's Disease Foundation and National Institutes of Health(NIH) Grant NS 041234 (to K.E.G.); NIH Grant NS 041234 (to H.S.X.); the China Ministry of Science and Technology Science Fund for Creative Research Group of China Grants 2012CB837701 and 2012YQ03026005, and National Natural Science Foundation of China Grant 91432114 (to M.L.); NIH Grant AG 036738 (to N.J.J.); and Northwestern Memorial Foundation Parkinson's Disease and Movement Disorders Advisory Council Grant, American Parkinson Disease Association, and NIH Grants NS 069777, NS 069777-S1, and NS 047085 (to C.S.C.). We thank Ellie Hong, Bonnie Erjavec, Jason Barraza, Yu Chen, Michael Fiske, and Thomas Madathany for their technical assistance; and members of the Chan laboratory for discussions. We also thank Eileen McIver and Dr. Mark Bevan for sharing their DREADD virus and experience with chemogenetic experiments. Finally, we thank Drs. Vandana Chinwalla and Sanza Kazadi from the Illinois Mathematics and Science Academy for their opportunity for the partnership with the SIR program
Keywords
- 6-OHDA
- Arkypallidal neurons
- Extrinsic inhibition
- Npas1-Cre
- Pallidostriatal projection
ASJC Scopus subject areas
- General Neuroscience