Local circuit neurons in the striatum regulate neural and behavioral responses to dopaminergic stimulation.
Interneurons are critical for shaping neuronal circuit activity in many parts of the central nervous system. To study interneuron function in the basal ganglia, we tested and characterized an NK-1 receptor-based method for targeted ablation of specific classes of interneuron in the striatum. Our findings demonstrate that the neurotoxin SP-PE35, a substance P-Pseudomonas exotoxin conjugate, selectively targets striatal cholinergic and nitric oxide synthase/somatostatinergic interneurons when injected locally into the striatum. The effects of this selective cell targeting encompassed alterations in both behavioral and neural responses to dopaminergic stimulation, including altered patterns of early-gene response in striosomes and matrix. We conclude that NK-1-bearing local circuit neurons of the striatum regulate the differential responses of striatal projection neurons to dopamine-mediated signaling.
Saka
E
E
Department of Brain and Cognitive Sciences and The McGovern Institute for Brain Research, Massachusetts Institute of Technology, E25-618, 45 Carleton Street, Cambridge, MA 02139, USA.
Iadarola
M
M
Fitzgerald
D J
DJ
Graybiel
A M
AM
D000818:Animals; D001522:Behavior, Animal; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D009498:Neurotoxins / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D013239:Stereotyped Behavior / Q000187:drug effects
D018491:Dopamine Agonists; D009498:Neurotoxins; D019001:Nitric Oxide Synthase; D004298:Dopamine