@article{9653dbe1cb224b0786a72c0572e8da1b,
title = "CalDAG-GEFI mediates striatal cholinergic modulation of dendritic excitability, synaptic plasticity and psychomotor behaviors",
abstract = "CalDAG-GEFI (CDGI) is a protein highly enriched in the striatum, particularly in the principal spiny projection neurons (SPNs). CDGI is strongly down-regulated in two hyperkinetic conditions related to striatal dysfunction: Huntington's disease and levodopa-induced dyskinesia in Parkinson's disease. We demonstrate that genetic deletion of CDGI in mice disrupts dendritic, but not somatic, M1 muscarinic receptors (M1Rs) signaling in indirect pathway SPNs. Loss of CDGI reduced temporal integration of excitatory postsynaptic potentials at dendritic glutamatergic synapses and impaired the induction of activity-dependent long-term potentiation. CDGI deletion selectively increased psychostimulant-induced repetitive behaviors, disrupted sequence learning, and eliminated M1R blockade of cocaine self-administration. These findings place CDGI as a major, but previously unrecognized, mediator of cholinergic signaling in the striatum. The effects of CDGI deletion on the self-administration of drugs of abuse and its marked alterations in hyperkinetic extrapyramidal disorders highlight CDGI's therapeutic potential.",
keywords = "Animals, Basal Ganglia Diseases/genetics, Central Nervous System Stimulants/pharmacology, Dendrites, Excitatory Postsynaptic Potentials/genetics, Guanine Nucleotide Exchange Factors/genetics, Hyperkinesis/genetics, Long-Term Potentiation, Male, Mice, Mice, Knockout, Motor Activity, Neostriatum/physiopathology, Neuronal Plasticity, Parasympathetic Nervous System/physiopathology, Polymorphism, Single Nucleotide, Receptor, Muscarinic M1/genetics, Substance-Related Disorders/genetics, Synapses",
author = "Crittenden, {Jill R} and Shenyu Zhai and Magdalena Sauvage and Takashi Kitsukawa and Eric Burgui{\`e}re and Morgane Thomsen and Hui Zhang and Cinzia Costa and Giuseppina Martella and Veronica Ghiglieri and Barbara Picconi and Pescatore, {Karen A} and Unterwald, {Ellen M} and Jackson, {Walker S} and Housman, {David E} and Caine, {S Barak} and David Sulzer and Paolo Calabresi and Smith, {Anne C} and Surmeier, {D James} and Graybiel, {Ann M}",
note = "Copyright {\textcopyright} 2018. Published by Elsevier Inc.",
year = "2021",
month = oct,
doi = "10.1016/j.nbd.2021.105473",
language = "English",
volume = "158",
journal = "Neurobiology of Disease",
issn = "0969-9961",
publisher = "Academic Press",
}