Cholinergic modulation of Kir2 channels selectively elevates dendritic excitability in striatopallidal neurons.
Dopamine-depleting lesions of the striatum that mimic Parkinson's disease induce a profound pruning of spines and glutamatergic synapses in striatopallidal medium spiny neurons, leaving striatonigral medium spiny neurons intact. The mechanisms that underlie this cell type-specific loss of connectivity are poorly understood. The Kir2 K(+) channel is an important determinant of dendritic excitability in these cells. Here we show that opening of these channels is potently reduced by signaling through M1 muscarinic receptors in striatopallidal neurons, but not in striatonigral neurons. This asymmetry could be attributed to differences in the subunit composition of Kir2 channels. Dopamine depletion alters the subunit composition further, rendering Kir2 channels in striatopallidal neurons even more susceptible to modulation. Reduced opening of Kir2 channels enhances dendritic excitability and synaptic integration. This cell type-specific enhancement of dendritic excitability is an essential trigger for synaptic pruning after dopamine depletion, as pruning was prevented by genetic deletion of M1 muscarinic receptors.
Shen
Weixing
W
Department of Physiology and Institute of Neuroscience, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Ave., Chicago, Illinois 60611, USA.
Tian
Xinyong
X
Day
Michelle
M
Ulrich
Sasha
S
Tkatch
Tatiana
T
Nathanson
Neil M
NM
Surmeier
D James
DJ
D000818:Animals; D000831:Animals, Newborn; D003342:Corpus Striatum / Q000166:cytology*; D003712:Dendrites / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009116:Muscarine / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects / Q000648:ultrastructure*; D016627:Oxidopamine / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology*; D043643:Receptor, Muscarinic M1 / Q000172:deficiency / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012110:Reserpine / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D018721:Muscarinic Agonists; D024661:Potassium Channels, Inwardly Rectifying; D043643:Receptor, Muscarinic M1; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D049452:Green Fluorescent Proteins; D009116:Muscarine; D012110:Reserpine; D016627:Oxidopamine