Nocturnal Running Research Articles

GABAA receptor subunit composition regulates circadian rhythms in rest–wake and synchrony among cells in the suprachiasmatic nucleus

The mammalian circadian clock located in the suprachiasmatic nucleus (SCN) produces robust daily rhythms including rest-wake. SCN neurons synthesize and respond to γ-aminobutyric acid (GABA), but its role remains unresolved. We tested the hypothesis that γ2- and δ-subunits of the GABAA receptor in the SCN differ in their regulation of synchrony among circadian cells. We used two approaches: 1) shRNA to knock-down (KD) the expression of either γ2 or δ subunits in the SCN or 2) knock-in mice harboring a point mutation in the M2 domains of the endogenous GABAA γ2 or δ subunits. KD of either γ2 or δ subunits in the SCN increased daytime running and reduced nocturnal running by reducing their circadian amplitude by a third. Similarly, δ subunit knock-in mice showed decreased circadian amplitude, increased duration of daily activity, and decreased total daily activity. Reduction, or mutation of either γ2 or δ subunits halved the synchrony among, and amplitude of, circadian SCN cells as measured by firing rate or expression of the PERIOD2 protein, in vitro. Surprisingly, overexpression of the γ2 subunit rescued these phenotypes following KD or mutation of the δ subunit, and overexpression of the δ subunit rescued deficiencies due to γ2 subunit KD or mutation. We conclude that γ2 and δ GABAA receptor subunits play similar roles in maintaining circadian synchrony in the SCN and amplitude of daily rest-wake rhythms, but that modulation of their relative densities can change the duration and amplitude of daily activities.

Female sex mitigates motor and behavioural phenotypes in TDP-43Q331K knock-in mice

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are overlapping neurodegenerative disorders. ALS is more commonly seen in men than women and the same may be the case for FTD. Preclinical models demonstrating sex-specific vulnerability may help to understand female resistance to ALS-FTD and thereby identify routes to therapy. We previously characterised a TDP-43Q331K knock-in mouse, which demonstrated behavioural phenotypes reminiscent of ALS-FTD in males. Here we present our behavioural observations of female TDP-43Q331K mutants. Female TDP-43Q331K knock-in mice displayed increased weight relative to wild-type and increased food intake at 20 months of age, much later than previously observed in male mutants. Spontaneous digging behaviour was initially normal and only declined in mutants in the second year of life. Gait analysis using Catwalk (https://www.noldus.com/catwalk-xt) found significant deficits in the second year of life, while nocturnal running behaviour was attenuated from ~ 250 days of life. These results indicate that while female TDP-43Q331K knock-in mice do display progressive behavioural phenotypes, these are less severe than we previously noted in male mutants. Further studies of male and female TDP-43Q331K knock-in mice may help to unravel the mechanisms underlying sex-specific vulnerability in ALS-FTD.

Rat Running Wheel Behavior Reflects Inflammatory, Orofacial Pain

Background: Our objective was to establish a novel, unbiased metric of inflammatory, orofacial pain. Method: Rats were placed individually into cages equipped with running wheels, and allowed an acclimation period of 17 days. Diurnal and nocturnal voluntary running behaviors were recorded. After day 17, rats were deeply anesthetized and divided into mustard oil, vehicle (mineral oil) and drug (ibuprofen) groups. Injections of mustard oil or mineral oil were made into the vestibule superior to the maxillary molar. Running wheel behavior was recorded for three days following the procedure. Results: After acclimation, the average percentage of running behavior that occurred at night was 94% +/-1% SE. Mustard oil injections caused externally observable, unilateral inflammation. On average, mustard oil injections significantly reduced nocturnal running on the first and second nocturnal periods post-injection. The non-steroidal anti-inflammatory, ibuprofen, significantly improved running behavior during the second nocturnal period, which was abolished when removed during the third nocturnal period. Conclusions: We conclude that unilateral injections of algogens in the vestibule coupled with analysis of nocturnal running behavior is an effective method to measure acute inflammatory pain for three days that mirrors many painful clinical situations. The model could be used as inexpensive, quantitative method to evaluate putative pain relieving therapeutics.

Suprachiasmatic vasopressin and the circadian regulation of voluntary locomotor behavior.

A role for arginine vasopressin in the circadian regulation of voluntary locomotor behavior (wheel running activity) was investigated in the golden hamster, Mesocricetus auratus. Spontaneous nocturnal running was suppressed in a dose-dependent manner by systemic injections of vasopressin, and also in a concentration-dependent manner by microinjections directly into the hypothalamic suprachiasmatic nucleus. Pre-injections of a vasopressin V1 receptor antagonist into the nucleus reduced the suppression of behavior by vasopressin. Ethogram analyses revealed that peripheral drug injections predominantly increased grooming, flank marking, and sleep-related behaviors. Central injections did not induce sleep, but increased grooming and periods of 'quiet vigilance' (awake but not moving). Nocturnal behavioral profiles following either peripheral or central injections were similar to those shown by untreated animals in the hour prior to the onset of nocturnal wheel running. Site control vasopressin injections into the medial preoptic area or periaqueductal gray increased flank marking and grooming, but had no significant effect on locomotion, suggesting behavioral specificity of a vasopressin target near the suprachiasmatic nucleus. Both peripheral and central administration increased FOS-like immunoreactivity in the retinorecipient core of the suprachiasmatic nucleus. The distribution of FOS-positive cells overlapped the calbindin subregion, but was more extensive, and most calbindin-positive cells did not co-express FOS. We propose a model of temporal behavioral regulation wherein voluntary behavior, such as nocturnal locomotor activity, is inhibited by the activity of neurons in the suprachiasmatic ventrolateral core that project to the posterior hypothalamus and are driven by rhythmic vasopressin input from the dorsomedial shell.

The Thalamic Intergeniculate Leaflet Mediates Locomotor Activity-Induced Reversal of Phenotype in Photoperiod Nonresponsive Siberian Hamsters

The role of the intergeniculate leaflet of the thalamus (IGL) in photoperiod responsiveness was examined in a laboratory-selected line of photoperiod nonresponsive (NR) Siberian hamsters. NR hamsters fail to exhibit typical winter-type responses (i.e., gonadal regression and development of winter-type pelage) when exposed to short day lengths (e.g., 10 h of light/day). Earlier studies revealed that NR hamsters will exhibit winter-type responses when exposed to short photoperiod if they are given free access to a running wheel. The present study tested the hypothesis that this locomotor activity-induced reversal of phenotype is dependent on the IGL. Male NR hamsters underwent destruction of the IGL prior to being housed in short day lengths in cages equipped with running wheels. Activity rhythms were monitored for 8 weeks, after which time pelage response and paired testes weights were obtained. In contrast to sham-operated NR animals given access to running wheels, IGL-ablated animals showed no increase in the duration of nocturnal running wheel activity and became active later in the night than sham-lesioned animals. Lesioned animals also failed to exhibit the typical short photoperiod-induced gonadal regression and pelage molt. The results implicate the IGL in the mechanism by which running wheel activity can influence photoperiodic responses.

Composição da artropodofauna entomófoga associada a diferentes genótipos de sorgo granífero no cerrado do Sudeste do Brasil

Espécies de artrópodos entomófagos foram coletadas e identificadas nos genótipos sorgo AF-28, IAC-83/75-5-1-6, TX-2536, BR-300, IPA-201 e SAR, no Município de Selvíria, MS. Foram conduzidos três experimentos em campo, com os genótipos sendo semeados em 03/1988, 10/1988 e 02/1989, respectivamente. Para contagem dos artrópodos entomófagos, no início do florescimento foram marcadas 560 panículas por genótipo. Após esse momento, diariamente e durante 14 dias seguidos, foram coletadas 40 panículas por genótipo (10 por parcela). Nas coletas foram utilizados sacos plásticos com 10 litros de capacidade para envolver as panículas e capturar os artrópodos presentes. As panículas coletadas foram levadas para o Laboratório de Entomologia da Faculdade de Engenharia/UNESP, Campus de Ilha Solteira, SP, para separação, contagem e identificação dos artrópodos. Nas panículas provenientes da semeadura da seca coletou-se, em média, maior número de artrópodos entomófagos em relação à semeadura das águas. Dos artrópodos entomófagos coletados, as aranhas apresentaram maior número de espécies e, desses, a tecelã Alpaida veniliae (Keys.), a aranha corredora noturna Cheiracanthium inclusum (Blackwall), e a caçadora de emboscada, Misumenops pallidus (Keys.), foram as mais abundantes. O genótipo de sorgo IPA-201 comportou-se como o mais atrativo ao percevejo Orius sp. e à tesourinha Doru lineare (Eschs.), enquanto que o IAC-83/75-5-1-6 foi medianamente atrativo a D. lineare. As aranhas foram coletadas em maior número nos genótipos BR-300 e SART.

Activity rhythms in female montane voles (Microtus montanus)

Seasonal changes in activity patterns have been reported in several species of arvicoline (= microtine) rodents in the wild. Adult male montane voles (Microtus montanus) shift from predominantly nocturnal running wheel use under long photoperiod to predominantly diurnal running wheel use under short photoperiod. Under the same conditions, females also increase diurnal activity under short photoperiod. However, females display more variability in activity patterns under long photoperiod than do males.

Variations in running activity and enzymatic adaptations in voluntary running rats

The running behavior and biochemical markers of oxidative and glycolytic activities associated with voluntary running activity were studied in male Sprague-Dawley rats after 6 wk of training in exercise wheel cages. Twenty-four-hour recordings of running activity were used to quantify the number of individual running bouts, their duration and running speed, and the distance run per day. We then established three categories of voluntary running activity based on the mean distance run per day during the last 3 wk of training: low-activity runners averaged 2-5 km/day, medium runners 6-9 km/day, and high runners greater than 11 km/day. Each group demonstrated an intermittent, nocturnal running pattern, at relatively high intensities, with a similar mean running speed for all groups (avg approximately 45 m/min). Differences in total distance run per day were the result of variations in both the number and duration of individual running bouts. Specifically, high runners (n = 7) had 206 +/- 30 individual running bouts per 24 h, each lasting 87 +/- 7 s; medium runners (n = 7) 221 +/- 22 running bouts, lasting 47 +/- 5 s; and low runners (n = 7) 113 +/- 7 bouts, each lasting 40 +/- 7 s. Voluntary running depressed the rate of body weight gain compared with sedentary control rats, despite an increased food and water intake for all runners. Furthermore, drinking activity was temporally associated with running periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Opiate-receptor blockade reduces voluntary running but not self-stimulation in hamsters

Naltrexone HCl, a long-acting opiate receptor blocker was administered to female hamsters at two doses, 10 and 20 mg/kg, IP prior to 12 hr of nocturnal running or every 12 hr during access to hypothalamic self-stimulation to determine whether endogenous opiates played a role in either of these two motivated behaviors. Naltrexone suppressed total running activity and speed, and caused an increase in pause time but did not affect the rate of hypothalamic self-stimulation. Furthermore, weight gain was unaffected by four weeks of self-stimulation but was accelerated during two weeks of voluntary running. Thus stimulation of endogenous opiate receptors helps support high levels of voluntary running but is not involved in initiation of running or in maintenance of intracranial self-stimulation in female hamsters. Furthermore, the association of opiate receptor stimulation and increased somatic growth with voluntary running but not with self-stimulation suggests a possible facilitatory role for endogenous opiates in acceleration of growth by exercise.