Interactive Effects of Dorsomedial Hypothalamic Nucleus and Time-Restricted Feeding on Fractal Motor Activity Regulation

Abstract

One evolutionary adaptation in motor activity control of animals is the anticipation of food that drives foraging under natural conditions and is mimicked in laboratory with daily scheduled food availability. Food anticipation is characterized by increased activity a few hours before the feeding period. Here we report that 2-h food availability during the normal inactive phase of rats not only increases activity levels before the feeding period but also alters the temporal organization of motor activity fluctuations over a wide range of time scales from minutes up to 24 h. We demonstrate this multiscale alteration by assessing fractal patterns in motor activity fluctuations-similar fluctuation structure at different time scales-that are robust in intact animals with ad libitum food access but are disrupted under food restriction. In addition, we show that fractal activity patterns in rats with ad libitum food access are also perturbed by lesion of the dorsomedial hypothalamic (DMH)-a neural node that is involved in food anticipatory behavior. Instead of further disrupting fractal regulation, food restriction restores the disrupted fractal patterns in these animals after the DMH lesion despite the persistence of the 24-h rhythms. This compensatory effect of food restriction is more clearly pronounced in the same animals after the additional lesion of the suprachiasmatic nucleus (SCN)-the central master clock in the circadian system that generates and orchestrates circadian rhythms in behavior and physiological functions in synchrony with day-night cycles. Moreover, all observed influences of food restriction persist even when data during the food anticipatory and feeding period are excluded. These results indicate that food restriction impacts dynamics of motor activity at different time scales across the entire circadian/daily cycle, which is likely caused by the competition between the food-induced time cue and the light-entrained circadian rhythm of the SCN. The differential impacts of food restriction on fractal activity control in intact and DMH-lesioned animals suggest that the DMH plays a crucial role in integrating these different time cues to the circadian network for multiscale regulation of motor activity.

Keywords: circadian rhythm; dorsomedial hypothalamic nucleus; food anticipation; fractal regulation; motor activity; suprachiasmatic nucleus.

Figure 1

Representative locomotor activity recordings and their averaged daily profiles of rats under 12 h:12 h light-dark cycles. (A) Recordings of an intact rat, a rat with the lesion of DMH (DMHx rat), and the same DMH-lesion rat after an additional lesion of the SCN with ad libitum food access. Gray (white) bars indicate the dark (light) periods of the light-dark cycle. (B) Recordings of an intact rat and a DMHx rat (the same as in A) before and after the SCN lesion with restricted food availability. Food was available daily for 2 h at 6–7 h after light on in each cycle (brown bars). (C) The averaged 24-h activity waveforms of the recordings in (A). (D) The averaged 24-h waveforms of the recordings in (B). To obtain the 24-h activity patterns, data were first normalized by daily means and then averaged across different days. The increased activity levels 3 h before the feeding period (green dashed boxes) indicate food-anticipatory activity (FAA).

Figure 2

Influence of food restriction on fractal activity patterns in intact animals and in animals after the lesions of the SCN and the DMH. Fluctuation functions of intact animals (A), a rat after the DMH lesion (B), and the same rat (as in B) after the lesions of the DMH and the SCN (C). Data are shown on log-log plots. Fluctuation functions are vertically shifted for a better visualization of the influence of food restriction. Results were obtained from the signals shown in Figure 1 using the detrended fluctuation analysis. (D) Scaling exponents at time scales > 4 h. ^* indicates the effect of food restriction: ^*p ≤ 0.02 and ^**p ≤ 0.002. ^#indicates the difference between large (>4 h) and small time scales (<4 h): ^#p ≤ 0.02, ^##p ≤ 0.002 and ^###p ≤ 0.0002.

Figure 3

Schematic diagram of the control network for fractal activity regulation. (A,B) In addition to the SCN, the DMH is required for fractal activity regulation in intact rats with free access to food. Lesioninng the DMH led to disrupted fractal regulation as characterized by significantly reduced correlations at >4 h (B). (C,D) Restricted food access during the normal inactive periods (light phase of the light-dark cycles) had opposite impacts on fractal activity regulation in intact animals (i.e., causing a reduction in correlations at >4 h) and in DMH-lesioned animals (i.e., causing an increase in correlations at >4 h), despite the similar influences on 24-h activity rhythms (i.e., food-anticipatory activity and reduced amplitude of 24-h rhythm).