SUMMARY Ballistic tongue projection in toads is a remarkably fast and powerful movement. The goals of this study were to: (1) quantify in vivo power output and activity of the depressor mandibulae muscles that are responsible for ballistic mouth opening, which powers tongue projection; (2) quantify the elastic properties of the depressor mandibulae muscles and their series connective tissues using in situ muscle stimulation and force-lever studies; and (3) develop and test an elastic recoil model, based on the observed elastic properties of the depressor mandibulae muscles and series connective tissues, that accounts for displacement, velocity, acceleration and power output during ballistic mouth opening in toads. The results demonstrate that the depressor mandibulae muscles of toads are active for up to 250 ms prior to mouth opening. During this time, strains of up to 21.4% muscle resting length (ML) develop in the muscles and series connective tissues. At maximum isometric force, series connective tissues develop strains up to 14% ML, and the muscle itself develops strains up to 17.5%ML. When the mouth opens rapidly, the peak instantaneous power output of the depressor mandibulae muscles and series connective tissues can reach 9600 W kg–1. The results suggest that: (1) elastic recoil of muscle itself can contribute significantly to the power of ballistic movements; (2) strain in series elastic elements of the depressor mandibulae muscle is too large to be borne entirely by the cross bridges and the actin–myosin filament lattice; and (3) central nervous control of ballistic tongue projection in toads likely requires the specification of relatively few parameters.

Hypoglossal motoneurons (XII MNs) control muscles of the mammalian tongue and are rhythmically active during breathing. Acetylcholine (ACh) modulates XII MN activity by promoting the release of glutamate from neurons that express nicotinic ACh receptors (nAChRs). Chronic nicotine exposure alters nAChRs on neurons throughout the brain, including brain stem respiratory neurons. Here we test the hypothesis that developmental nicotine exposure (DNE) reduces excitatory synaptic input to XII MNs. Voltage-clamp experiments in rhythmically active medullary slices showed that the frequency of excitatory postsynaptic currents (EPSCs) onto XII MNs from DNE animals is reduced by 61% (DNE = 1.7 ± 0.4 events/s; control = 4.4 ± 0.6 events/s; P < 0.002). We also examine the intrinsic excitability of XII MNs to test whether cells from DNE animals have altered membrane properties. Current-clamp experiments showed XII MNs from DNE animals had higher intrinsic excitability, as evaluated by measuring their response to injected current. DNE cells had high-input resistances (DNE = 131.9 ± 13.7 MΩ, control = 78.6 ± 9.7 MΩ, P < 0.008), began firing at lower current levels (DNE = 144 ± 22 pA, control = 351 ± 45 pA, P < 0.003), and exhibited higher frequency-current gain values (DNE = 0.087 ± 0.012 Hz/pA, control = 0.050 ± 0.004 Hz/pA, P < 0.02). Taken together, our data show previously unreported effects of DNE on XII MN function and may also help to explain the association between DNE and the incidence of central and obstructive apneas.

Developmental nicotine exposure (DNE) impacts central respiratory control in neonates born to smoking mothers. We previously showed that DNE enhances the respiratory motor response to bath application of AMPA to the brainstem, although it was unclear which brainstem respiratory neurons mediated these effects (Pilarski and Fregosi, 2009). Here we examine how DNE influences AMPA-type glutamatergic neurotransmission in the pre-Bötzinger complex (pre-BötC) and the hypoglossal motor nucleus (XIIMN), which are neuronal populations located in the medulla that are necessary for normal breathing. Using rhythmic brainstem slices from neonatal rats, we microinjected AMPA into the pre-BötC or the XIIMN while recording from XII nerve rootlets (XIIn) as an index of respiratory motor output. DNE increased the duration of tonic activity and reduced rhythmic burst amplitude after AMPA microinjection into the XIIMN. Also, DNE led to an increase in respiratory burst frequency after AMPA injection into the pre-BötC. Whole-cell patch-clamp recordings of XII motoneurons showed that DNE increased motoneuron excitability but did not change inward currents. Immunohistochemical studies indicate that DNE reduced the expression of glutamate receptor subunits 2 and 3 (GluR2/3) in the XIIMN and the pre-BötC. Our data show that DNE alters AMPAergic synaptic transmission in both the XIIMN and pre-BötC, although the mechanism by which this occurs is unclear. We suggest that the DNE-induced reduction in GluR2/3 may represent an attempt to compensate for increased cell excitability, consistent with mechanisms underlying homeostatic plasticity.

This review is a comprehensive description of all muscles that assist lung inflation or deflation in any way. The developmental origin, anatomical orientation, mechanical action, innervation, and pattern of activation are described for each respiratory muscle fulfilling this broad definition. In addition, the circumstances in which each muscle is called upon to assist ventilation are discussed. The number of “respiratory” muscles is large, and the coordination of respiratory muscles with “nonrespiratory” muscles and in nonrespiratory activities is complex—commensurate with the diversity of activities that humans pursue, including sleep (8.27). The capacity for speech and adoption of the bipedal posture in human evolution has resulted in patterns of respiratory muscle activation that differ significantly from most other animals. A disproportionate number of respiratory muscles affect the nose, mouth, pharynx, and larynx, reflecting the vital importance of coordinated muscle activity to control upper airway patency during both wakefulness and sleep. The upright posture has freed the hands from locomotor functions, but the evolutionary history and ontogeny of forelimb muscles pervades the patterns of activation and the forces generated by these muscles during breathing. The distinction between respiratory and nonrespiratory muscles is artificial, as many “nonrespiratory” muscles can augment breathing under conditions of high ventilator demand. Understanding the ontogeny, innervation, activation patterns, and functions of respiratory muscles is clinically useful, particularly in sleep medicine. Detailed explorations of how the nervous system controls the multiple muscles required for successful completion of respiratory behaviors will continue to be a fruitful area of investigation. © 2019 American Physiological Society. Compr Physiol 9:1025‐1080, 2019.

There is mounting evidence that neonatal animals exposed to nicotine in the prenatal period exhibit a variety of anatomic and functional abnormalities that adversely affect their respiratory and cardiovascular control systems, but how nicotine causes these developmental alterations is unknown. The principle that guides our work is that PNE impairs the ability of nicotinic acetylcholine receptors (nAChRs) to modulate the pre-synaptic release of both inhibitory (particularly GABA) and excitatory (glutamate) neurotransmitters, leading to marked alterations in the density and/or function of receptors on the (post-synaptic) membrane of respiratory neurons. Such changes could lead to impaired ventilatory responses to sensory afferent stimulation, and altered breathing patterns, including central apneic events. In this brief review we summarize the work that lead to the development of this hypothesis, and introduce some new data that support and extend it.