On-Going Frontal Alpha Rhythms Are Dominant in Passive State and Desynchronize in Active State in Adult Gray Mouse Lemurs

The gray mouse lemur (Microcebus murinus) is considered a useful primate model for translational research. In the framework of IMI PharmaCog project (Grant Agreement n°115009, www.pharmacog.org), we tested the hypothesis that spectral electroencephalographic (EEG) markers of motor and locomotor activity in gray mouse lemurs reflect typical movement-related desynchronization of alpha rhythms (about 8–12 Hz) in humans. To this aim, EEG (bipolar electrodes in frontal cortex) and electromyographic (EMG; bipolar electrodes sutured in neck muscles) data were recorded in 13 male adult (about 3 years) lemurs. Artifact-free EEG segments during active state (gross movements, exploratory movements or locomotor activity) and awake passive state (no sleep) were selected on the basis of instrumental measures of animal behavior, and were used as an input for EEG power density analysis. Results showed a clear peak of EEG power density at alpha range (7–9 Hz) during passive state. During active state, there was a reduction in alpha power density (8–12 Hz) and an increase of power density at slow frequencies (1–4 Hz). Relative EMG activity was related to EEG power density at 2–4 Hz (positive correlation) and at 8–12 Hz (negative correlation). These results suggest for the first time that the primate gray mouse lemurs and humans may share basic neurophysiologic mechanisms of synchronization of frontal alpha rhythms in awake passive state and their desynchronization during motor and locomotor activity. These EEG markers may be an ideal experimental model for translational basic (motor science) and applied (pharmacological and non-pharmacological interventions) research in Neurophysiology.     

Age‐Related Effects on the Biological Clock and its Behavioral Output in a Primate

In humans, activity rhythms become fragmented and attenuated in the elderly. This suggests an alteration of the circadian system per se that could in turn affect the expression of biological rhythms. In primates, very few studies have analyzed the effect of aging on the circadian system. The mouse lemur provides a unique model of aging in non‐human primates. To assess the effect of aging on the circadian system of this primate, we recorded the circadian and daily rhythms of locomotor activity of mouse lemurs of various ages. We also examined age‐related changes in the daily rhythm of immunoreactivities for vasoactive intestinal polypeptide (VIP) and arginine‐vasopressin (AVP) in suprachiasmatic nucleus neurons (SCN), two major peptides of the biological clock. Compared to adult animals, aged mouse lemurs showed a significant increase in daytime activity and an advanced activity onset. Moreover, when maintained in constant dim red light, aged animals exhibited a shortening of the free‐running period compared to adult animals. In adults, AVP immunoreactivity (ir) peaked during the second part of the day, and VIP ir peaked during the night. In aged mouse lemurs, the peaks of AVP ir and VIP ir were significantly shifted with no change in amplitude. AVP ir was most intense at the beginning of the night; whereas, VIP ir peaked at the beginning of the daytime. A weakened oscillator could account for the rhythmic disorders often observed in the elderly. Changes in the daily rhythms of AVP ir and VIP ir may affect the ability of the SCN to transmit rhythmic information to other neural target sites, and thereby modify the expression of some biological rhythms.     

Exploration Behavior and Morphology are Correlated in Captive Gray Mouse Lemurs (<Emphasis Type="Italic">Microcebus murinus</Emphasis>)

Behavior varies among individuals and is flexible within individuals. However, studies of behavioral syndromes and animal personality have demonstrated that animals can show consistency in their behavior and as such may be restricted in their behavioral responses. Like any other trait, including morphology, performance, or physiology, personality is now considered an important component of ecology and may have fitness consequences. Moreover, in some species personality correlates with other traits, as predicted in the context of a recent theoretical framework postulating that individual differences in growth and body size can affect behavior through effects on growth–mortality tradeoffs. This “pace of life” hypothesis predicts that animals that explore more should be larger and have higher growth rates than those that explore less. We tested for associations between morphology and a behavioral trait in a captive colony of gray mouse lemurs (Microcebus murinus). We used open-field tests to evaluate exploration behavior and measured a series of morphological traits in 72 individuals (32 males and 40 females). Our results show that the latency to start exploring correlates positively with adult body size and body weight at birth. These data provide evidence for a link between morphology and behavior in this species, thus supporting predictions of dispersal models but diverging from the predictions of the “pace of life” model.     

Chronic food shortage and seasonal modulations of daily torpor and locomotor activity in the grey mouse lemur (Microcebus murinus)

The extent to which seasonal plasticity in torpor displayed by one of the smallest Malagasy primates (Microcebus murinus) will help survival in the context of ongoing global change-induced chronic food shortage, is unknown. Body temperature (Tb) and locomotor activity were measured by telemetry in short- (SD, winter-acclimated) and long-days (LD, summer-acclimated) males (n = 24) during an experimental 35-day calorie restriction of 40 or 80%. Under SD exposure, regardless of calorie restriction intensity, mouse lemurs immediately increased torpor depth and duration by 4.6-fold, and showed greater phase-advanced entry into torpor (2.4-fold). Tb adjustments were efficient under 40% calorie restriction to maintain body mass, whereas they did not prevent a 0.71 +/- 0.11 g/day mass loss during 80% calorie restriction. The 40% food-deprived LD animals combined an early shallow deepening of torpor (1 degrees C) and a late 18% decrease in locomotor activity, resulting in a moderate 6% mass loss. After 15 days of 80% calorie restriction, LD animals exhibited a SD phenotype by increasing their torpor duration and phase-advancing the entry of torpor (16 min/day). Those adjustments had no impact on mass loss (0.93 +/- 0.07 g/day) as locomotor activity increased four-fold. Daily torpor allows M. murinus to face moderate food shortage whatever the photoperiod but poorly mitigates energy imbalance during severe food deprivation, especially under LD exposure. Although the behavioral thermoregulation role warrants further investigation in energy savings, M. murinus survival would be impaired during long-term food shortage in summer.     

Olfactory bulbectomy modifies photic entrainment and circadian rhythms of body temperature and locomotor activity in a nocturnal primate

Studies on rodents have emphasized that removal of the olfactory bulbs modulates circadian rhythmicity. Using telemetric recordings of both body temperature (Tb) and locomotor activity (LA) in a male nocturnal primate, the gray mouse lemur, the authors investigated the effects of olfactory bulbectomy on (1) the circadian periods of Tb and LA in constant dim light condition, and (2) photic re-entrainment rates of circadian rhythms following 6-h phase shifts of entrained light-dark cycle (LD 12:12). Under free-running condition, bulbectomized males had significantly shorter circadian periods of Tb and LA rhythms than those of control males. However, the profiles of Tb rhythms, characterized by a phase of hypothermia at the beginning of the subjective day, and Tb parameters were not modified by olfactory bulbectomy. Under a light-dark cycle, olfactory bulbectomy significantly modified the expression of daily hypothermia, especially by an increase in the latency to reach minimal daily Tb, suggesting a delayed response to induction of daily hypothermia by light onset. Reentrainment rates following both a 6-h phase advance and a 6-h phase delay of entrained LD were also delayed in bulbectomized males. Olfactory bulbectomy led to significant fragmentation of locomotor activity and increased locomotor activity levels during the resting period. The shortening of circadian periods in bulbectomized males could partly explain the delayed responses to photic stimuli since in control males, the longer the circadian period, the better the response to light entrainment. This experiment shows for the 1st time that olfactory bulbs can markedly modify the circadian system in a primate.     

Shortened seasonal photoperiodic cycles accelerate aging of the diurnal and circadian locomotor activity rhythms in a primate

The gray mouse lemur (Microcebus murinus), a prosimian primate, exhibits seasonal rhythms strictly controlled by photoperiodic variations. Previous studies indicated that longevity can be altered by long-term acceleration of seasonal rhythms, providing a model for assessing various aspects of aging. To assess the effect of aging and accelerated aging on the circadian system of this primate, we compared the circadian rhythm of the locomotor activity in adult mouse lemurs (2-4.5 years, n = 9), aged mouse lemurs (5-9 years, n = 10), and adult mouse lemurs that had been exposed from birth to a shortened seasonal photoperiodic cycle (2-4.5 years, n = 7). Compared to adult animals, aged mouse lemurs showed a significant increase in intradaily variability and an advanced activity onset. Aging was characterized by a decrease in amplitude, with both a decrease in nocturnal activity and an increase in daytime activity. When maintained in constant dim red light, aged animals exhibited a shortening of the free-running period (22.8 +/- 0.1 h) compared to adult animals (23.5 +/- 0.1 h). A 3- to 5-year exposure to an accelerated seasonal photoperiodic rhythm ("annual" duration of 5 months) in accelerated mouse lemurs produced disturbances of the locomotor activity rhythm that resembled those of aged mouse lemurs, whether animals were studied in entrained or in free-running conditions. The present study demonstrated a weakened and fragmented locomotor activity rhythm during normal aging in this primate. Increasing the number of expressed seasonal cycles accelerated aging of parameters related to circadian rhythmicity in adult animals.     

Thermoregulatory responses to variations of photoperiod and ambient temperature in the male lesser mouse lemur: a primitive or an advanced adaptive character?

The lesser mouse lemur, a small Malagasy primate, is exposed to strong seasonal variations in ambient temperature and food availability in its natural habitat. To face these environmental constraints, this nocturnal primate exhibits biological seasonal rhythms that are photoperiodically driven. To determine the role of daylength on thermoregulatory responses to changes in ambient temperature, evaporative water loss (EWL), body temperature (T _b) and oxygen consumption, measured as resting metabolic rate (RMR), were measured in response to ambient temperatures ranging from 5 °C to 35 °C, in eight males exposed to either short (10L:14D) or long (14L:10D) daylengths in controlled captive conditions. In both photoperiods, EWL, T _b and RMR were significantly modified by ambient temperatures. Exposure to ambient temperatures below 25 °C was associated with a decrease in T _b and an increase in RMR, whereas EWL remained constant. Heat exposure caused an increase in T _b and heat loss through evaporative pathways. Thermoregulatory responses to changes in ambient temperature significantly differed according to daylength. Daily variations in T _b and EWL were characterized by high values during the night. During the diurnal rest, lower values were found and a phase of heterothermia occurred in the early morning followed by a spontaneous rewarming. The amplitude of T _b decrease with or without the occurrence of torpor (T _b < 33 °C) was dependent on both ambient temperature and photoperiod. This would support the hypothesis of advanced thermoregulatory processes in mouse lemurs in response to selective environmental pressure, the major external cue being photoperiodic variations. Accepted: 4 August 1998     

How Aging Affects Grasping Behavior and Pull Strength in Captive Gray Mouse Lemurs (<Emphasis Type="Italic">Microcebus murinus</Emphasis>)

Prehension is essential for animal survival and fitness. It is involved in locomotion and feeding behavior and subject to physical and physiological constraints. Studies of prehension in primates have explored the importance of food properties and of the environment, but aging has rarely been studied although prehensile capacity may deteriorate with age in humans. To test the hypothesis that aging affects grasping abilities and to reveal possible behavioral adaptations to this, we quantified behavioral grasping strategies and pull strength in 10 young adult (2–3 yr old) and 10 aged (7–8 yr old) gray mouse lemurs (Microcebus murinus). We assessed grasping strategies in an experimental cage by quantifying grip types used to grasp static and mobile foods. We measured strength using a Kistler triaxial force platform. Our results show that 1) mobile and static foods affected individuals of different ages in similar ways; 2) older individuals used more mouth grasps than young ones; 3) aged individuals made twice as many attempts as young ones when grasping mobile food items but this difference was not significant; and 4) there were no differences in hand grip strength between age classes but young individuals showed a higher foot pull strength compared to old ones. These data suggest that the observed differences in behavior may be due to a decrease in foot grip strength, which in turn influences stability on narrow branches, forcing animals to use their hands to maintain stability and preventing them from using their hands for food-related tasks.     

The Grey Mouse Lemur Uses Season-Dependent Fat or Protein Sparing Strategies to Face Chronic Food Restriction

During moderate calorie restriction (CR) the heterotherm Microcebus murinus is able to maintain a stable energy balance whatever the season, even if only wintering animals enter into torpor. To understand its energy saving strategies to respond to food shortages, we assessed protein and energy metabolisms associated with wintering torpor expression or summering torpor avoidance. We investigated body composition, whole body protein turnover, and daily energy expenditure (DEE), during a graded (40 and 80%) 35-day CR in short-days (winter; SD40 and SD80, respectively) and long-days (summer; LD40 and LD80, respectively) acclimated animals. LD40 animals showed no change in fat mass (FM) but a 12% fat free mass (FFM) reduction. Protein balance being positive after CR, the FFM loss was early and rapid. The 25% DEE reduction, in LD40 group was mainly explained by FFM changes. LD80 animals showed a steady body mass loss and were excluded from the CR trial at day 22, reaching a survival-threatened body mass. No data were available for this group. SD40 animals significantly decreased their FM level by 21%, but maintained FFM. Protein sparing was achieved through a 35 and 39% decrease in protein synthesis and catabolism (protein turnover), respectively, overall maintaining nitrogen balance. The 21% reduction in energy requirement was explained by the 30% nitrogen flux drop but also by torpor as DEE FFM-adjusted remained 13% lower compared to ad-libitum. SD80 animals were unable to maintain energy and nitrogen balances, losing both FM and FFM. Thus summering mouse lemurs equilibrate energy balance by a rapid loss of active metabolic mass without using torpor, whereas wintering animals spare protein and energy through increased torpor expression. Both strategies have direct fitness implication: 1) to maintain activities at a lower body size during the mating season and 2) to preserve an optimal wintering muscle mass and function.