Long‐term Potentiation in the Striatum is Unmasked by Removing the Voltage‐dependent Magnesium Block of NMDA Receptor Channels

Abstract

We have studied the effects of tetanic stimulation of the corticostriatal pathway on the amplitude of striatal excitatory synaptic potentials. Recordings were obtained from a corticostriatal slice preparation by utilizing both extracellular and intracellular techniques. Under the control condition (1.2 mM external Mg²⁺), excitatory postsynaptic potentials (EPSPs) evoked by cortical stimulation were reversibly blocked by 10 μM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), an antagonist of dl-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) ionotropic glutamate receptors, while they were not affected by 30–50 μM 2-amino-5-phosphonovalerate (APV), an antagonist of N-methyl-d-aspartate (NMDA) glutamate receptors. In the presence of 1.2 mM external Mg²⁺, tetanic activation of cortical inputs produced long-term depression (LTD) of both extracellularly and intracellularly recorded synaptic potentials. When Mg²⁺ was removed from the external medium, EPSP amplitude and duration increased. In Mg²⁺-free medium, cortically evoked EPSPs revealed an APV-sensitive component; in this condition tetanic stimulation produced long-term potentiation (LTP) of synaptic transmission. Incubation of the slices in 30–50 μM APV blocked striatal LTP, while it did not affect LTD. In Mg²⁺-free medium, incubation of the slices in 10 μM CNQX did not block the expression of striatal LTP. Intrinsic membrane properties (membrane potential, input resistance and firing pattern) of striatal neurons were altered neither by tetanic stimuli inducing LTD and LTP, nor by removal of Mg²⁺ from the external medium. These findings show that repetitive activation of cortical inputs can induce long-term changes of synaptic transmission in the striatum. Under control conditions NMDA receptor channels are inactivated by the voltage-dependent Mg²⁺ block and repetitive cortical stimulation induces LTD which does not require activation of NMDA channels. Removal of external Mg²⁺ deinactivates these channels and reveals a component of the EPSP which is potentiated by repetitive activation. Since the striatum has been involved in memory and in the storage of motor skills, LTD and LTP of synaptic transmission in this structure may provide the cellular substrate for motor learning and underlie the physiopathology of some movement disorders.