Physiological and anatomical properties of the suprachiasmatic nucleus of an anophthalmic mouse

Abstract

Congenitally anophthalmic mice (ZRDCT-AN) have circadian rhythms which ‘free-run’ and are not light modulated. Their rhythms differ from those of controls in: duration of circadian period, length of active phase, and pattern/intensity of activity. Three different populations have been described based upon wheel-running: rhythmic with stable period, rhythmic with unstable period and arrhythmic. Circadian rhythms are generated by neurons in the suprachiasmatic nuclei (SCN) of the hypothalamus. To better understand whether intrinsic properties of SCN neurons differ in anophthalmic and sighted mice, we examined the electrical activity of these neurons in slices, using single unit recordings, ionophoresis and bath perfusion of agonists and antagonists of known SCN neurotransmitters. Lucifer yellow was injected to characterize morphology. In controls, in daytime, units fired at a higher rate (44% at ≥5 Hz) than at night (21% at ≥5 Hz) and with regular interspike intervals versus irregular intervals nocturnally. In anophthalmics four firing patterns were observed as follows: (1) irregular at <5 spikes/s (70% of the total); (2) regular at ≥5 spikes/s; (<10%); (3) irregular bursts (20%); (4) regular bursts (<1%). Most neurons were inhibited by GABA, but a few were excited in controls. Blocking synaptic transmission with low Ca 2+/high Mg 2+ increased the frequency and regularized the pattern of previously irregular discharges both in anophthalmics and controls. Bicuculline (10 −5 M), a GABA A antagonist, had a similar effect. These data suggest that the characteristic irregular firing pattern of anophthalmics, and of controls at night, results from extrinsic, at least in part, GABAergic input.