Daily replacement of very high-fat diet stabilizes food intake and improves mouse welfare by ensuring food quality.

Researchers are obligated to ensure food quality and provide laboratory animals with a palatable diet. Factors influencing the quality and palatability of very high-fat diet (VHFD), a widely used rodent diet, however, are understudied. We conducted experiments to establish best practices for ensuring the quality of VHFD and to improve mouse welfare.

Basal Forebrain Parvalbumin Neurons Mediate Arousals from Sleep Induced by Hypercarbia or Auditory Stimuli.

The ability to rapidly arouse from sleep is important for survival. However, increased arousals in patients with sleep apnea and other disorders prevent restful sleep and contribute to cognitive, metabolic, and physiologic dysfunction [1, 2]. Little is currently known about which neural systems mediate these brief arousals, hindering the development of treatments that restore normal sleep.

Learning and memory are impaired in the object recognition task during metestrus/diestrus and after sleep deprivation.

Females are an under-represented research model and the mechanisms through which sleep loss impairs cognition are not clear. Since levels of reproductive hormones and the estrous cycle are sensitive to sleep loss and necessary for learning and memory, we hypothesized that sleep deprivation impacts learning and memory in female mice by interfering with the estrous cycle. We used the object recognition task to assess learning and memory in female mice during separate phases of the estrous cycle and after sleep loss.

Isoflurane produces antidepressant effects and induces TrkB signaling in rodents.

A brief burst-suppressing isoflurane anesthesia has been shown to rapidly alleviate symptoms of depression in a subset of patients, but the neurobiological basis of these observations remains obscure. We show that a single isoflurane anesthesia produces antidepressant-like behavioural effects in the learned helplessness paradigm and regulates molecular events implicated in the mechanism of action of rapid-acting antidepressant ketamine: activation of brain-derived neurotrophic factor (BDNF) receptor TrkB, facilitation of mammalian target of rapamycin (mTOR) signaling pathway and inhibition of glycogen synthase kinase 3β (GSK3β). Moreover, isoflurane affected neuronal plasticity by facilitating long-term potentiation in the hippocampus.

Hypothalamic dysfunction of the thrombospondin receptor α2δ-1 underlies the overeating and obesity triggered by brain-derived neurotrophic factor deficiency.

Brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, are critical components of the neural circuitry controlling appetite and body weight. Diminished BDNF signaling in mice results in severe hyperphagia and obesity. In humans, BDNF haploinsufficiency and the functional Bdnf Val66Met polymorphism have been linked to elevated food intake and body weight.

Weighing in the role of BDNF in the central control of eating behavior.

The prevalence of obesity and its associated medical complications, including type 2 diabetes and cardiovascular disease, continues to rise globally. Lifestyle changes in the last decades have greatly contributed to the current obesity trends. However, inheritable biological factors that disrupt the tightly regulated equilibrium between caloric intake and energy expenditure also appear to play a critical part.

Brain-derived neurotrophic factor regulates hedonic feeding by acting on the mesolimbic dopamine system.

Brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, play prominent roles in food intake regulation through central mechanisms. However, the neural circuits underlying their anorexigenic effects remain largely unknown. We showed previously that selective BDNF depletion in the ventromedial hypothalamus (VMH) of mice resulted in hyperphagic behavior and obesity.

c-Fos protein expression is increased in cholinergic neurons of the rodent basal forebrain during spontaneous and induced wakefulness.

It has been proposed that cholinergic neurons of the basal forebrain (BF) may play a role in vigilance state control. Since not all vigilance states have been studied, we evaluated cholinergic neuronal activation levels across spontaneously occurring states of vigilance, as well as during sleep deprivation and recovery sleep following sleep deprivation. Sleep deprivation was performed for 2h at the beginning of the light (inactive) period, by means of gentle sensory stimulation.

Assessing sleepiness in the rat: a multiple sleep latencies test compared to polysomnographic measures of sleepiness.

Sleepiness following 6 h of sleep deprivation (SD) was evaluated with a rat multiple sleep latencies test (rMSLT), and the findings were compared to conventional polysomnographic measures of sleepiness. The 6 h of SD was produced by automated activity wheels, and was terminated at either the end of the light period or at the beginning of the dark period. The rMSLT consisted of 5 min wakefulness induced by sensory stimulation followed by 25 min of freedom to sleep.

Experimental sleep fragmentation and sleep deprivation in rats increases exploration in an open field test of anxiety while increasing plasma corticosterone levels.

Sleep deprivation alters mood and anxiety in man. In rats, 24 h of treadmill-induced total sleep deprivation or sleep fragmentation increased exploratory behavior in an open field test of anxiety compared to cage or exercise controls. Plasma corticosterone (CORT) levels of sleep disturbed and exercise control rats were elevated compared to cage controls, suggesting that the increased exploration observed in the sleep disturbed rats was not due to a hypothalamic-pituitary-adrenal (HPA) stress response.

Depletion of central BDNF in mice impedes terminal differentiation of new granule neurons in the adult hippocampus.

Granule neurons generated in the adult mammalian hippocampus synaptically integrate to facilitate cognitive function and antidepressant efficacy. Here, we investigated the role of BDNF in facilitating their maturation in vivo. We found that depletion of central BDNF in mice elicited an increase in hippocampal cell proliferation without affecting cell survival or fate specification.

Sleep fragmentation elevates behavioral, electrographic and neurochemical measures of sleepiness.

Sleep fragmentation, a feature of sleep apnea as well as other sleep and medical/psychiatric disorders, is thought to lead to excessive daytime sleepiness. A rodent model of sleep fragmentation was developed (termed sleep interruption, SI), where rats were awakened every 2 min by the movement of an automated treadmill for either 6 or 24 h of exposure. The sleep pattern of rats exposed to 24 h of SI resembled sleep of the apneic patient in the following ways: sleep was fragmented (up to 30 awakening/h), total rapid eye movement (REM) sleep time was greatly reduced, non-rapid eye movement (NREM) sleep episode duration was reduced (from 2 min, 5 s baseline to 58 s during SI), whereas the total amount of NREM sleep time per 24 h approached basal levels.