Facilitated Glutamatergic Transmission in the Striatum of D2 Dopamine Receptor-Deficient Mice

• Published in: Journal of neurophysiology 2001-02, Vol.85 (2), p.659-670
• Main Authors: Cepeda, C, Hurst, R. S, Altemus, K. L, Flores-Hernandez, J, Calvert, C. R, Jokel, E. S, Grandy, D. K, Low, M. J, Rubinstein, M, Ariano, M. A, Levine, M. S
• Format: Article
• Language: English
• Subjects: 4-Aminopyridine - pharmacology; Animals; Corpus Striatum - cytology; Corpus Striatum - physiology; Dopamine - pharmacology; Electrophysiology; Glutamic Acid - physiology; Immunohistochemistry; In Vitro Techniques; Membranes - physiology; Mice; Mice, Inbred C57BL; Mice, Knockout - genetics; Neurons - drug effects; Neurons - ultrastructure; Receptors, Dopamine D2 - agonists; Receptors, Dopamine D2 - deficiency; Receptors, Dopamine D2 - genetics; Receptors, Dopamine D2 - physiology; Synapses - drug effects; Synapses - physiology; Synaptic Transmission - physiology
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.2001.85.2.659

  1 Mental Retardation Research Center, University of California, Los Angeles, California 90095;   2 Department of Cell and Developmental Biology and   3 Vollum Institute, Oregon Health Sciences University, Portland, Oregon 97201;   4 Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas and Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina; and   5 Department of Neuroscience, The Chicago Medical School, North Chicago, Illinois 60064 Cepeda, C., R. S. Hurst, K. L. Altemus, J. Flores-Hernández, C. R. Calvert, E. S. Jokel, D. K. Grandy, M. J. Low, M. Rubinstein, M. A. Ariano, and M. S. Levine. Facilitated Glutamatergic Transmission in the Striatum of D 2 Dopamine Receptor-Deficient Mice. J. Neurophysiol. 85: 659-670, 2001. Dopamine (DA) receptors play an important role in the modulation of excitability and the responsiveness of neurons to activation of excitatory amino acid receptors in the striatum. In the present study, we utilized mice with genetic deletion of D 2 or D 4 DA receptors and their wild-type (WT) controls to examine if the absence of either receptor subtype affects striatal excitatory synaptic activity. Immunocytochemical analysis verified the absence of D 2 or D 4 protein expression in the striatum of receptor-deficient mutant animals. Sharp electrode current- and whole cell patch voltage-clamp recordings were obtained from slices of receptor-deficient and WT mice. Basic membrane properties were similar in D 2 and D 4 receptor-deficient mutants and their respective WT controls. In current-clamp recordings in WT animals, very little low-amplitude spontaneous synaptic activity was observed. The frequency of these spontaneous events was increased slightly in D 2 receptor-deficient mice. In addition, large-amplitude depolarizations were observed in a subset of neurons from only the D 2 receptor-deficient mutants. Bath application of the K + channel blocker 4-aminopyridine (100 µM) and bicuculline methiodide (10 µM, to block synaptic activity due to activation of GABA A receptors) markedly increased spontaneous synaptic activity in receptor-deficient mutants and WTs. Under these conditions, D 2 receptor-deficient mice displayed significantly more excitatory synaptic activity than their WT controls, while there was no difference between D 4 receptor-deficient mice and their controls. I