title: Functional disturbances in the striatum by region-specific ablation of NMDA receptors.
abstract: To study the role of NMDA receptors in dopamine signaling of the striatum, the brain area that receives glutamatergic inputs from various cortical areas and most dopaminergic inputs, we generated striatum-specific NMDA receptor-deficient mice. The mutant pups showed reduced food intake and retarded growth starting at the second postnatal week and died on approximately postnatal day 20 (P20). The time course of postnatal lethality is similar to that of compound mutant, double knockout of dopamine D1/D2 receptors, or genetically engineered dopamine-deficient mouse. In vivo electrophysiological recordings in the mutant pups showed that frequencies in the range of gamma oscillation were reduced in the striatal circuits. Moreover, the number of functional dopamine receptors in the striatum as measured by D1- and D2-binding experiments was greatly diminished in the mutants as compared with control animals. A consequence of diminished dopamine binding in the striatum manifested in an increase of locomotor activity. The administration of D1/D2 agonists paradoxically reduced the hyperactivity of the mutant mice as compared with an increase in locomotor activity in control mice. These results demonstrate that the NMDA receptor plays an essential role in the integration of dopamine signaling in the striatum and that is required in behavioral function.
authors: Center for Systems Neurobiology, Department of Pharmacology, Boston University School of Medicine, Boston, MA 02118, USA.
authors: Nobuhisa
authors: N
authors: Ohtsuka
authors: Morris F
authors: MF
authors: Tansky
authors: Hui
authors: H
authors: Kuang
authors: Saïd
authors: S
authors: Kourrich
authors: Mark J
authors: MJ
authors: Thomas
authors: John L R
authors: JL
authors: Rubenstein
authors: Marc
authors: M
authors: Ekker
authors: Susan E
authors: SE
authors: Leeman
authors: Joe Z
authors: JZ
authors: Tsien
mesh_terms: D000200:Action Potentials; D000818:Animals; D000831:Animals, Newborn; D004594:Electrophysiology; D017353:Gene Deletion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity; D017072:Neostriatum / Q000473:pathology*; D009928:Organ Specificity; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D009435:Synaptic Transmission
chemical_list: C409466:NR1 NMDA receptor; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate