Effects of excitatory amino acid receptor antagonists and agonists on suprachiasmatic nucleus responses to retinohypothalamic tract volleys

A slice preparation of the mouse hypothalamus that includes the suprachiasmatic nuclei (SCN), the optic chiasm and the optic nerves was used for pharmacologic investigations of the nature of the receptors mediating the excitation of SCN neurons by input from the retinohypothalamic tract (RHT). Bath application of cis-2,3-piperidinedicarboxylic acid, a non-selective antagonist of excitatory amino acid receptors, reversibly blocked the postsynaptic component of the field potentials evoked in the dorsolateral SCN by stimulation of the optic nerve. The selective antagonist of N-methyl-D-aspartate receptors, 2-amino-5-phosphonovaleric acid, had no effect on SCN responses. Glutamic acid diethyl ester and 2-amino-4-phosphonobutyric acid also were without effect, but gamma-D-glutamylglycine caused a small decrease in the amplitude of the postsynaptic wave. Addition of the agonists, kainate and N-methyl-D,L-aspartate, to the superfusate also blocked the postsynaptic response. Kainate was the most potent agonist. L-Glutamate was without effect at up to 100 microM. These results indicate that postsynaptic responses in the SCN to retinohypothalamic tract volleys are mediated by a non-NMDA class of excitatory amino acid receptors.