Human hypoglossal motor unit activities in exercise.

The genioglossus (GG) muscle is considered the principal protruder muscle of the tongue that dilates and stiffens the pharyngeal airway. We recorded whole muscle and single motor unit (MU) activities in healthy adults performing progressive intensity exercise on a cycle ergometer. Tungsten microelectrodes were inserted percutaneously into the GG of 11 subjects (20-40 years) to record electromyographic (EMG) activities and pulmonary ventilation (VI) at rest and at workload increments up to 300 W. Increases in respiratory drive were associated with increases in VI, mean inspiratory flow (Vt/Ti) and tonic and phasic components of the GG EMG activity. In contrast, individual MUs typically showed expiration-related decreases in firing as exercise intensity increased. We suggest the decrease in MU activity may occur secondary to afferent feedback from lungs/chest wall and that compensation for more negative inspiratory airway pressures generated during heavy exercise occurs primarily via recruitment of previously silent MUs.

The Eating-Disorder Associated HDAC4A778T Mutation Alters Feeding Behaviors in Female Mice.

BACKGROUND: While eating disorders (EDs) are thought to result from a combination of environmental and psychological stressors superimposed on genetic vulnerability, the neurobiological basis of EDs remains incompletely understood. We recently reported that a rare missense mutation in the gene for the transcriptional repressor histone deacetylase 4 (HDAC4) is associated with the risk of developing an ED in humans. METHODS: To understand the biological consequences of this missense mutation, we created transgenic mice carrying this mutation by introducing the alanine to threonine mutation at position 778 of mouse Hdac4 (corresponding to position 786 of the human protein). Bioinformatic analysis to identify Hdac4-regulated genes was performed using available databases. RESULTS: Male mice heterozygous for HDAC4A778T did not show any metabolic or behavioral differences. In contrast, female mice heterozygous for HDAC4A778T display several ED-related feeding and behavioral deficits depending on housing condition. Individually housed HDAC4A778T female mice exhibit reduced effortful responding for high-fat diet and compulsive grooming, whereas group-housed female mice display increased weight gain on high-fat diet, reduced behavioral despair, and increased anxiety-like behaviors. Bioinformatic analysis identifies mitochondrial biogenesis including synthesis of glutamate/gamma-aminobutyric acid as a potential transcriptional target of HDAC4A778T activity relevant to the behavioral deficits identified in this new mouse model of disordered eating. CONCLUSIONS: The HDAC4A778T mouse line is a novel model of ED-related behaviors and identifies mitochondrial biogenesis as a potential molecular pathway contributing to behavioral deficits.

Evaluating the control: minipump implantation and breathing behavior in the neonatal rat.

We evaluated genioglossus (GG) gross motoneuron morphology, electromyographic (EMG) activities, and respiratory patterning in rat pups allowed to develop without interference (unexposed) and pups born to dams subjected to osmotic minipump implantation in utero (saline-exposed). In experiment 1, 48 Sprague-Dawley rat pups (Charles-River Laboratories), ages postnatal day 7 (P7) through postnatal day 10 (P10), were drawn from two experimental groups, saline-exposed (n = 24) and unexposed (n = 24), and studied on P7, P8, P9, or P10. Pups in both groups were sedated (Inactin hydrate, 70 mg/kg), and fine-wire electrodes were inserted into the GG muscle of the tongue and intercostal muscles to record EMG activities during breathing in air and at three levels of normoxic hypercapnia [inspired CO2 fraction (FiCO2 ): 0.03, 0.06, and 0.09]. Using this approach, we assessed breathing frequency, heart rate, apnea type, respiratory event types, and respiratory stability. In experiment 2, 16 rat pups were drawn from the same experimental groups, saline-exposed (n = 9) and unexposed (n = 7), and used in motoneuron-labeling studies. In these pups a retrograde dye was injected into the GG muscle, and the brain stems were subsequently harvested and sliced. Labeled GG motoneurons were identified with microscopy, impaled, and filled with Lucifer yellow. Double-labeled motoneurons were reconstructed, and the number of primary projections and soma volumes were calculated. Whereas pups in each group exhibited the same number (P = 0.226) and duration (P = 0.093) of respiratory event types and comparable motoneuron morphologies, pups in the implant group exhibited more central apneas and respiratory instability relative to pups allowed to develop without interference.

Developmental nicotine exposure adversely effects respiratory patterning in the barbiturate anesthetized neonatal rat.

Neonates at risk for sudden infant death syndrome (SIDS) are hospitalized for cardiorespiratory monitoring however, monitoring is costly and generates large quantities of averaged data that serve as poor predictors of infant risk. In this study we used a traditional autocorrelation function (ACF) testing its suitability as a tool to detect subtle alterations in respiratory patterning in vivo. We applied the ACF to chest wall motion tracings obtained from rat pups in the period corresponding to the mid-to-end of the third trimester of human pregnancy. Pups were drawn from two groups: nicotine-exposed and saline-exposed at each age (i.e., P7, P8, P9, and P10). Respiratory-related motions of the chest wall were recorded in room air and in response to an arousal stimulus (FIO2 14%). The autocorrelation function was used to determine measures of breathing rate and respiratory patterning. Unlike alternative tools such as Poincare plots that depict an averaged difference in a measure breath to breath, the ACF when applied to a digitized chest wall trace yields an instantaneous sample of data points that can be used to compare (data) points at the same time in the next breath or in any subsequent number of breaths. The moment-to-moment evaluation of chest wall motion detected subtle differences in respiratory pattern in rat pups exposed to nicotine in utero and aged matched saline-exposed peers. The ACF can be applied online as well as to existing data sets and requires comparatively short sampling windows (∼2 min). As shown here, the ACF could be used to identify factors that precipitate or minimize instability and thus, offers a quantitative measure of risk in vulnerable populations.

Neural drive to respiratory muscles in the spontaneously breathing rat pup.

The neonatal rodent serves as useful and appropriate model within which to study respiratory system development. Despite an extensive literature that documents respiratory control in vitro, in vivo studies have relied upon whole body plethysmography to determine measures of respiratory frequency and tidal volume. However, plethysmography restricts access to the animal and thus, respiratory muscle electromyographic (EMG) activities have not been recorded in these studies previously. Electromyography yields accurate information about neural respiratory center output to the musculature and therefore, about the control of breathing in the intact animal. In this case, we documented neural drive to respiratory pump and upper airway muscles, electrocardiogram (ECG) and chest wall motions in rat pups up to 10 days of age noting sighs, spontaneous central apneas and hypopneas in room air and with successive increments in fractional inspired CO2 (FICO2). Our findings underscore the advantages of EMG recordings for purposes of determining the magnitude and distribution of neural drive to respiratory muscles and for characterizing the full range of breathing behaviors exhibited by rats in the early postnatal period.