title: Npas1+ Pallidal Neurons Target Striatal Projection Neurons.
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.
  
  
  
  An anatomical projection from the pallidum to the striatum has been described for decades, but little is known about its connectivity pattern. The authors dissect the presynaptic and postsynaptic neurons involved in this projection, and show its cell-specific remodeling and strengthening in parkinsonian mice. Chemogenetic activation of Npas1(+) pallidal neurons that give rise to the principal pallidostriatal projection increases the time that the mice spend motionless. This argues that maladaptive strengthening of this connection underlies the paucity of volitional movements, which is a hallmark of Parkinson's disease.
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611.
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Glajch
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611.
authors.forename: Daniel A
authors.identifier: 0000-0001-9136-5440
authors.initials: DA
authors.lastname: Kelver
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Hegeman
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611.
authors.forename: Qiaoling
authors.initials: Q
authors.lastname: Cui
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611.
authors.forename: Harry S
authors.identifier: 0000-0002-9502-0973
authors.initials: HS
authors.lastname: Xenias
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Augustine
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611.
authors.forename: Vivian M
authors.initials: VM
authors.lastname: Hernández
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611.
authors.forename: Neha
authors.initials: N
authors.lastname: Verma
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611.
authors.forename: Tina Y
authors.initials: TY
authors.lastname: Huang
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China, School of Life Sciences, Tsinghua University, Beijing 100084, China, and.
authors.forename: Minmin
authors.identifier: 0000-0003-3535-6624
authors.initials: M
authors.lastname: Luo
authors.affiliation: Institute of Molecular Medicine, University of Texas, Houston, Texas 77030.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Justice
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, saviochan@gmail.com.
authors.forename: C Savio
authors.identifier: 0000-0002-3474-1718
authors.initials: CS
authors.lastname: Chan
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D005917:Globus Pallidus / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D062308:Optogenetics; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D055366:Synaptic Potentials
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; C512770:Npas1 protein, mouse
keywords: 6-OHDA; Npas1-Cre; arkypallidal neurons; extrinsic inhibition; pallidostriatal projection