Activation of hamster suprachiasmatic neurons in vitro via metabotropic glutamate receptors

The neurophysiological effects of ionophoretic application of the metabotropic glutamate receptor agonist (1S,3R)-1-amino-1,3-cyclopentanedicarboxylic acid on the firing rate of single suprachiasmatic nucleus cells was studied in a hypothalamic slice preparation. In addition, the effects of the phenylglycine derivative (RS)-alpha-methyl-4-carboxyphenylglycine, a selective metabotropic glutamate receptor antagonist on responses evoked by (1S,3R)-1-amino-1,3-cyclopentanedicarboxylic acid and N-methyl-D-aspartate were assessed. (1S,3R)-1-Amino-1,3-cyclopentanedicarboxylic acid elicited current-dependent increases in neuronal activity in 65% of all suprachiasmatic nucleus cells studied, while N-methyl-D-aspartate activated 93% of the same cells. Cells in the ventrolateral suprachiasmatic nucleus were more sensitive to (1S,3R)-1-amino-1,3-cyclopentanedicarboxylic acid application (82% of cells activated) than those in the dorsomedial suprachiasmatic nucleus (28% of cells activated). In addition, responses evoked by (1S,3R)-1-amino-1,3-cyclopentanedicarboxylic acid in the ventrolateral suprachiasmatic nucleus had a rapid onset and a prolonged recovery from agonist application, whereas responses elicited in the dorsomedial suprachiasmatic nucleus were slower in onset and recovered more quickly from agonist application. Co-application of (RS)-alpha-methyl-4-carboxyphenylglycine selectively attenuated (1S,3R)-1-amino-1,3-cyclopentanedicarboxylic acid-evoked responses but had no effect on N-methyl-D-aspartate-evoked activity in the same cells. These results indicate that (1S,3R)-1-amino-1,3-cyclopentanedicarboxylic acid application activates single cells in the hamster suprachiasmatic nucleus and these responses are selectively attenuated by (RS)-alpha-methyl-4-carboxyphenylglycine. Cells in the ventrolateral suprachiasmatic nucleus are more sensitive to (1S,3R)-1-amino-1,3-cyclopentanedicarboxylic acid application than those in the dorsomedial suprachiasmatic nucleus. These results are the first demonstration that metabotropic glutamate receptors can modulate spontaneous neuronal activity within the suprachiasmatic nucleus, the predominant mammalian circadian pacemaker.