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Volume 17, Number 12, Issue of June 15, 1997 pp. 4536-4544
Copyright ©1997 Society for Neuroscience

Abnormal Synaptic Plasticity in the Striatum of Mice Lacking Dopamine D2 Receptors

Received Jan. 8, 1997; revised March 25, 1997; accepted March 28, 1997.

Paolo Calabresi¹, Adolfo Saiardi³, Antonio Pisani¹, Ja-Hyun Baik³, Diego Centonze¹, Nicola B. Mercuri^{1, 2}, Giorgio Bernardi^{1, 2}, and Emiliana Borrelli³

¹ Clinica Neurologica, Universitá di Roma Tor Vergata, Dipartimento Sanitá, 00173 Rome, Italy, ² Ospedale S. Lucia, Via Ardeatina, Rome, Italy, and ³ Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Médicale/Université Louis Pasteur, 67404 Illkirch Cedex, Strasbourg, France

Dopamine D2 receptors (D2Rs) are of crucial importance in the striatal processing of motor information received from the cortex. Disruption of the D2R gene function in mice results in a severe locomotor impairment. This phenotype has analogies with Parkinson's disease symptoms. D2R-null mice were used to investigate the role of this receptor in the generation of striatal synaptic plasticity. Tetanic stimulation of corticostriatal fibers produced long-term depression (LTD) of EPSPs in slices from wild-type (WT) mice. Strikingly, recordings from D2R-null mice showed the converse: long-term potentiation (LTP). This LTP, unlike LTD, was blocked by an NMDA receptor antagonist. In magnesium-free medium, LTP was also revealed in WT mice and found to be enhanced by L-sulpiride, a D2R antagonist, whereas it was reversed into LTD by LY 17555, a D2R agonist. In D2R-null mice this modulation was lost. Thus, our study indicates that D2Rs play a key role in mechanisms underlying the direction of long-term changes in synaptic efficacy in the striatum. It also shows that an imbalance between D2R and NMDA receptor activity induces altered synaptic plasticity at corticostriatal synapses. This abnormal synaptic plasticity might cause the movement disorders observed in Parkinson's disease.

Key words: LTD; LTP; synaptic plasticity; striatum; dopamine; NMDA; dopamine D2 receptor; D2 receptor knock-out mice

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