The hypothalamic suprachiasmatic nucleus (SCN, the clock nucleus) is a part of a network regulating feeding and metabolism. The hypothalamic arcuate nucleus (ARCN) may be involved in food intake regulation while the SCN modulates the timing of feeding. The input to the SCN from the retrochiasmatic area of the ARCN provides a route by which the SCN may be influenced by neuroendocrine cues. The SCN has been reported to contain receptors to leptin (Hakansson et al. 1998), the peptide secreted by adipose tissue and involved in the modulation of the neural control of feeding. The aim of the present study was to determine if leptin influenced the activity of cells in the SCN or their responses to stimulation of the ARCN.

Conventional extracellular recordings were made from single units in the SCN in 500 Ám sagittal hypothalamic slices of brains removed from anaesthetised (urethane 1.2 g/kg I.P.) male Wistar rats and their responses to ARCN stimulation were assessed by peristimulus time histograms.

A total of 24 of the 35 SCN cells responded to stimulation of the ARCN. Excitatory (n = 12), inhibitory (n = 7), and complex responses (excitation followed by inhibition or vice versa; n = 5) were seen. The responses had a short latency (< 20 ms) after the stimulus pulse. Typically excitatory responses had a short duration (▓le│25 ms) and inhibitory responses were longer (▓ge│40 ms). After the administration of leptin (20 nM) the mean spike frequency of SCN cells was reduced (P < 0.001, Wilcoxon signed rank test) while mean log interspike interval (ISI) was increased in duration (P = 0.033, Wilcoxon signed rank test). The entropy of the log ISI probability distribution was also increased by 0.16 ± 0.07 (mean difference ± S.E.M., P = 0.033, paired t test) a change in the regularity of the recorded spike train. The input to the SCN from the ARCN was significantly influenced by leptin in 12 of 35 experiments. Excitatory responses were reduced in 7 cases and increased in 2 cases. In one case an excitatory response became evident only in the presence of leptin. Leptin did not appear to alter inhibitory responses that were seen before its administration but in two experiments inhibitory responses became evident only in the presence of leptin. The effects of leptin developed relatively slowly (> 10 min) and in most cases were completely or partially reversible following washout with control solution for 20-30 min.

The present results show that leptin can influence the activity of SCN units and modulate the input to the SCN from the ARCN. The effects of leptin involved both a change in the regularity of the ISI of the spike trains recorded from SCN neurons and a reduction in their firing rate. The heterogeneity of the responses probably, reflects the diversity of cell types in the SCN.

Hakansson ML et al. (1998). J Neurosci 18, 559-572.

This work was supported by the EPSRC.