Abstract
Knowledge of the neuronal membrane properties and synaptic physiology of the suprachiasmatic nucleus (SCN) is critical for an understanding of the cellular basis of circadian rhythms in mammals. The hypothalamic slice preparation from rodents and a combination of electrophysiological techniques (i.e., extracellular single- and multiple-unit recording, intracellular recording, and whole-cell patch clamp) were used to study (1) the role of excitatory and inhibitory amino acids (i.e., glutamate and γ-aminobutyric acid [GABA] in synaptic transmission, (2) the membrane properties of SCN neurons, and (3) the mechanisms of neuronal synchronization. Antagonists for N-methyl-D-aspartate (NMDA) receptors and non-NMDA receptors blocked excitatory postsynaptic potentials (EPSPs) evoked by stimulation of the optic nerve or other sites when SCN cells were depolarized or at rest, respectively. Bicuculline blocked inhibitory postsynaptic potentials (IPSPs) that were evoked by local stimulation or that occurred spontaneously. The IPSP reversal potential was near the C1- equilibrium potential, and was shifted to depolarized levels by raising intracellular [C1-]. Thus, glutamate and GABA appear to mediate fast excitatory and inhibitory synaptic transmission in the SCN. Some SCN neurons, but not all of them, had low-threshold Ca2+ spikes and time-dependent inward rectification, thus indicating that the electrical properties of SCN neurons are not homogenous. Neurons with a firing rate of >6 Hz had a regular pattern, and neurons with a rate of <4 Hz had an irregular pattern; since both the firing rate and pattern could be modified with injected currents, SCN neurons with different firing patterns are unlikely to represent distinct classes of cells. Synchronous bursts of action potentials occurred in the SCN after chemical synapses were blocked with [Ca2+]-free solutions and with amino acid transmitter antagonists, which indicates that synchronous neuronal activity can occur in the SCN without active chemical synapses and suggests that a different mechanism of communication exists in the SCN. Future in vitro electrophysiological experiments should provide an explanation of how neurotransmitters, local neuronal circuits, and intrinsic membrane properties regulate the electrical activity of SCN neurons during the circadian rhythm.