Mechanism of bilateral communication in the suprachiasmatic nucleus

The central circadian pacemaker of the suprachiasmatic nuclei ( SCN ) is a bilaterally symmetrical structure. Little is known about the physiological mechanisms underlying communication between the left and right SCN and yet the degree of synchronization between SCN neurons can have a critical impact on the properties of the circadian system. In this study, we used electrophysiological tools and calcium ( C a 2+ ) imaging to examine the mechanisms underlying bilateral signaling in mouse SCN . Electrical stimulation of one SCN produced responses in the contralateral SCN with a short delay (approximately 5 ms) and C a 2+ ‐dependence that are consistent with action potential‐mediated chemical synaptic transmission. Patch‐clamp recordings of stimulated cells revealed excitatory postsynaptic inward‐currents ( EPSC s), which were sufficient in magnitude to elicit action potentials. Electrical stimulation evoked tetrodotoxin‐dependent C a 2+ transients in about 30% of all contralateral SCN neurons recorded. The responding neurons were widely distributed within the SCN with a highest density in the posterior SCN . EPSC s and C a 2+ responses were significantly reduced after application of a glutamate receptor antagonist. Application of antagonists for receptors of other candidate transmitters inhibited the C a 2+ responses in some of the cells but overall the impact of these antagonists was variable. In a functional assay, electrical stimulation of the SCN produced phase shifts in the circadian rhythm in the frequency of multiunit activity rhythm in the contralateral SCN . These phase shifts were blocked by a glutamate receptor antagonist. Taken together, these results implicate glutamate as a transmitter required for communication between the left and right SCN .