mGluR5 ablation in cortical glutamatergic neurons increases novelty-induced locomotion.
The group I metabotropic glutamate receptor 5 (mGluR5) has been implicated in the pathology of various neurological disorders including schizophrenia, ADHD, and autism. mGluR5-dependent synaptic plasticity has been described at a variety of neural connections and its signaling has been implicated in several behaviors. These behaviors include locomotor reactivity to novel environment, sensorimotor gating, anxiety, and cognition. mGluR5 is expressed in glutamatergic neurons, inhibitory neurons, and glia in various brain regions. In this study, we show that deleting mGluR5 expression only in principal cortical neurons leads to defective cannabinoid receptor 1 (CB1R) dependent synaptic plasticity in the prefrontal cortex. These cortical glutamatergic mGluR5 knockout mice exhibit increased novelty-induced locomotion, and their locomotion can be further enhanced by treatment with the psychostimulant methylphenidate. Despite a modest reduction in repetitive behaviors, cortical glutamatergic mGluR5 knockout mice are normal in sensorimotor gating, anxiety, motor balance/learning and fear conditioning behaviors. These results show that mGluR5 signaling in cortical glutamatergic neurons is required for precisely modulating locomotor reactivity to a novel environment but not for sensorimotor gating, anxiety, motor coordination, several forms of learning or social interactions.
The Cain Foundation Laboratories, Baylor College of Medicine, Houston, Texas, USA.
Chris P
CP
Jew
Chia-Shan
CS
Wu
Hao
H
Sun
Jie
J
Zhu
Jui-Yen
JY
Huang
Dinghui
D
Yu
Nicholas J
NJ
Justice
Hui-Chen
HC
Lu
D000305:Adrenal Cortex Hormones / Q000097:blood; D000818:Animals; D015153:Blotting, Western; D004594:Electrophysiology; D005260:Female; D008124:Locomotion / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism; D064529:Receptor, Metabotropic Glutamate 5 / Q000235:genetics / Q000378:metabolism*
D000305:Adrenal Cortex Hormones; C543264:Cnr1 protein, rat; C578936:Grm5 protein, mouse; D043884:Receptor, Cannabinoid, CB1; D064529:Receptor, Metabotropic Glutamate 5