Age-related changes in electrophysiological properties of the mouse suprachiasmatic nucleus in vitro

doi:10.1016/j.brainresbull.2004.12.006

Brain Research Bulletin

Volume 65, Issue 2, 15 March 2005, Pages 149-154

https://doi.org/10.1016/j.brainresbull.2004.12.006 Get rights and content

Abstract

Endogenous biological rhythms are altered at several functional levels during aging. The major pacemaker driving biological rhythms in mammals is the suprachiasmatic nucleus of the hypothalamus. In the present study we used tissue slices from young and old mice to analyze the electrophysiological properties of the retinorecipient ventrolateral part of the suprachiasmatic nucleus. Loose patch and whole-cell recordings were performed during day and night. Both young and old mice displayed a significant variation between day and night in the mean firing rate of suprachiasmatic nucleus neurons. The proportion of cells not firing spontaneous action potentials showed a clear day/night rhythm in young but not in old animals, that had an elevated number of such silent cells during the day compared to young animals. Analysis of firing patterns revealed a more regular spontaneous firing during the day than during the night in the old mice, while there was no difference between day and night in young animals. The frequency of spontaneous inhibitory postsynaptic currents was reduced in ventrolateral suprachiasmatic nucleus neurons in the old animals. Since the inhibitory input to these neurons is mainly derived from within the suprachiasmatic nucleus, this reduction most likely reflects the greater proportion of silent cells found in old animals. The results show that the suprachiasmatic nucleus of old mice is subject to marked electrophysiological changes, which may contribute to physiological and behavioral changes associated with aging.

Introduction

The circadian timing system undergoes marked alterations in mammals during aging. These include weakened ability to synchronize with external stimuli, dampening and fragmentation in activity and temperature cycles, and disruptions in sleep patterns [29]. In mammals the suprachiasmatic nucleus (SCN) of the anterior hypothalamus is considered to be the major pacemaker for circadian oscillations. Whether or not age-related alterations in endogenous biological rhythms reflect primary disturbances in the machinery of the SCN remains to be clarified. On one hand, alterations in the cyclic expression of certain neuropeptides [4], [6], [10], [11], [22] as well as reductions in amplitudes and occurrence of aberrant peaks in the spontaneous firing activity [3], [24], [28] have indicated that properties of individual SCN neurons change with aging. On the other hand, in old rats the cycling of the clock genes Period and Cryptochrome in the SCN remains robust [2], [31], and the total number of neurons and mean somatic volume of the SCN are unchanged [17], which suggests that disruptions in circadian organization during aging could reflect changes at other levels of the circadian system. The importance of peripheral, extra-SCN oscillators has recently also come into focus [7] and age-related disturbances in the interactions between circadian oscillators have been suggested [31].

The ventrolateral, or core, part of the SCN receives retinal input, and neurons in this area express vasoactive intestinal polypeptide (VIP) [1]. VIP modulates inhibitory synaptic transmission in the SCN and shows circadian oscillations in its expression [8], [9]. Both responses to light [27], [32] and day/night oscillations of VIP [4], [6], [10], [11], [13] are altered during aging. Electrophysiological studies on the aged SCN have only been made on hamsters and rats previously [24], [28]. In those studies extracellular measurements were performed within the whole SCN, and both studies revealed a reduced amplitude of the rhythm of spontaneous firing. Considering the age-related changes in light responses and VIP expression that occur specifically in the ventrolateral SCN, we wanted to investigate if there are parallel changes in the electrophysiological properties of these neurons. We therefore performed cell attached and whole-cell recordings in the ventrolateral SCN of young and old mice, to study spontaneous firing at the single neuron level as well as synaptic transmission. We report that although the pattern of day/night firing frequencies is similar in the two age groups, there are significant differences at the cellular and synaptic levels.

Section snippets

Materials and methods

Male C57B/6 mice (B&K, Sollentuna, Sweden) were maintained on a 12/12 h light/dark cycle for at least 10 days before the experiments. All the animal procedures were conducted under institutional guidelines and local ethical committee approval. The entire research protocol adhered to the guidelines of the European Council Directive (86/609/EEC). Two light/dark regimes were used, one starting at 07:00 for the day measurements (Zeitgeber time (ZT) 4–10), and one starting at 22:00 for the night

Results

The spontaneous firing rate (SFR) of SCN neurons varied significantly between day and night in both young (2.6 ± 0.2 and 1.6 ± 0.2 Hz, respectively, p < 0.01) and old animals (3.0 ± 0.2 and 2.2 ± 0.2 Hz, respectively, p < 0.01) (Fig. 1D). Thus, a clear day/night rhythm existed in both groups. No significant differences were seen when young and old animals were compared, indicating that the slice procedure did not affect the physiological properties differently in the two groups. There was, however, a

Discussion

The circadian pacemaker in the SCN is composed of multiple oscillator cells with individual rhythms of electrical activity that become synchronized by synaptic coupling. This was initially observed in dispersed cultures of SCN neurons [30] and has later been demonstrated also in slice preparations [19], [25]. Long-term recordings of individual cells have shown that most SCN neurons alternate between active and silent states in a periodic manner, and in this way contribute to daily rhythms of

Acknowledgements

This study was supported by EC grant number QLK6-CT-2002-02258 (K.K.) and Loo och Hans Ostermans stiftelse (M.A.W.).

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Age-related changes in electrophysiological properties of the mouse suprachiasmatic nucleus in vitro

Abstract

Introduction

Section snippets

Materials and methods

Results

Discussion

Acknowledgements

Brain Res.

Neuroscience

Neurobiol. Aging

Brain Res. Mol. Brain Res.

Neurosci. Lett.

Neuron

Cell

Neurosci. Lett.

Brain Res.

Brain Res.

Neurobiol. Aging

Brain Res.

Neuron

Neuroscience

Circadian profile of Per gene mRNA expression in the suprachiasmatic nucleus, paraventricular nucleus, and pineal body of aged rats

J. Neurosci. Res.

Circadian modulation of membrane properties in slices of rat suprachiasmatic nucleus

Neuroreport