Motoneuron Firing Rate Research Articles

Motor unit loss and neuromuscular junction degeneration precede clinically diagnosed sarcopenia

Background: Degeneration of motoneuron and neuromuscular junctions (NMJ) and loss of motor units (MUs) contribute to age-related muscle wasting and weakness, leading to sarcopenia. However, these features have not been adequately investigated in humans. This study aimed to compare neuromuscular system integrity and function across different stages of sarcopenia, with a particular focus on NMJ stability and MU properties. We hypothesized that progressive impairment of the neuromuscular system would be a hallmark of the progression of sarcopenia. Methods: We recruited 42 healthy young individuals (Y) (aged 25.98±4.6 yr; 57% females) and 88 older individuals (aged 75.9±4.7 yr; 55% females). The older group underwent a sarcopenia screening according to the revised guidelines of the European Working Group on Sarcopenia in Older People (EWGSOP2). In all groups, knee extensor muscle force was evaluated by isometric dynamometry, muscle size by ultrasound and MUP properties by intramuscular electromyography (iEMG). MU number estimate (iMUNE) was also obtained. Blood samples and muscle biopsies were collected to assess biomarkers of neuromuscular degeneration. Results: 39 older individuals were non-sarcopenic (NS), 31 pre-sarcopenic (PS) and 18 sarcopenic (S). A progressive decline in quadriceps force, cross-sectional area and appendicular lean mass was detected with the different stages of sarcopenia. Handgrip force and short physical performance battery (SPPB) scores were also progressively reduced. iEMG recordings showed increased near fiber segment jitter in NS, PS and S compared to the Y group, highlighting a decreased NMJ transmission stability. Elevated concentration of serum C-terminal agrin fragment and altered Cav3 protein expression further supported the finding of age-related NMJ instability in all the older groups. The iMUNE was lower in all older groups, confirming age-related loss of MUs. Motoneuron firing rate was decreased in S vs Y. Age-related increases in MU potential complexity were also observed. These observations were accompanied by increased muscle denervation and axonal damage, respectively, indicated by the increase in NCAM-positive fibres and the increase in serum concentration of neurofilament light chain. Notably, most of these MU and NMJ parameters did not differ in older individuals with or without sarcopenia. Conclusion: Alterations in MU properties, axonal damage, altered innervation profile and NMJ instability are signatures of neuromuscular system ageing. These neuromuscular impairments are accompanied by muscle atrophy and weakness, however, they appear to precede clinically diagnosed sarcopenia, as they are already detectable in older NS individuals. These are important parameters to monitor in order to counteract these impairments and slow down the onset and progression of sarcopenia. The present work was funded by the PRIN project ‘NeuAge’ (2017CBF8NJ_001) to MVN and MAP and the Milky Way Foundation, the Baxter Foundation and the Li Ka Shing Foundation to HMB. EM was supported by the Stanford Wu Tsai Human Performance Institute fellowship and Marie Skłodowska-Curie Actions postdoctoral fellowship. We also acknowledge co-funding from Next Generation EU to MVN, in the context of the National Recovery and Resilience Plan, Investment PE8 — Project Age-It: “Ageing Well in an Ageing Society”. This resource was co-financed by the Next Generation EU [DM 1557 11.10.2022]. The views and opinions expressed are only those of the authors and do not necessarily reflect those of the European Union or the European Commission. Neither the European Union nor the European Commission can be held responsible for them. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Decreased GABAergic Neurotransmission Promotes Breathing Upon Emergence From Hibernation

The respiratory network must produce reliable output for an animal to survive. Although respiratory motor plasticity is well appreciated, how plasticity mechanisms work to promote robustness following environmental perturbations that disrupt breathing is less clear. During underwater hibernation, respiratory neurons of bullfrogs remain inactive for months, triggering a suite of compensatory mechanisms that aim to maintain respiratory function. We hypothesized that GABAergic inhibition would decrease following hibernation. In control animals, respiratory frequency was under control of GABAAR signaling. Specifically, block of GABAARs dose-dependently decreased respiratory burst frequency in the in vitro brainstem preparation (n=5 preparations). After hibernation, GABAA receptor block had little to no impact on respiratory burst frequency, suggesting the network was no longer reliant on GABAergic inhibition to maintain normal frequency (n=5 preparations). The loss of inhibition was specific to the respiratory network because non-respiratory motor activity and large seizure-like bursts were similarly triggered by GABAA receptor blockade in intact brainstem preparations from controls and hibernators. We next used a semi-intact preparation that maintains functional respiratory-synaptic input onto rhythmic motor neurons to identify compensatory changes in GABAergic tone at the level of the motor neuron. In controls, the firing rate of respiratory motoneurons was constrained by a phasic GABAAR tone because focal application of bicuculline, a GABAAR antagonist, led to an increase in phasic firing frequency (n=12 cells). After hibernation, this bicuculline-mediated increase in phasic firing frequency was attenuated suggesting phasic inhibition onto the motor neuron had decreased (n=9 cells). Brain slice recordings of identified vagal motor neurons revealed that postsynaptic GABAA receptor strength was unchanged following hibernation (n=16 control cells; n=16 hibernation cells). Taken together, our results suggest that GABAergic activity is decreased in premotor networks following hibernation. Despite this dramatic loss of GABAergic function, respiratory output from control preparations was indistinguishable from hibernators. To elucidate the functional impacts of loss of GABAergic activity, we tested the network’s ability to produce output at colder temperatures. In controls, respiratory output slowed as temperature decreased, with most networks nearly silent at 8 degrees Celsius (n=5 preparations). Interestingly, in controls low dose block of GABAA receptors promoted respiratory activity at cold temperatures, with frequency not statistically different than baseline at any temperature tested (n=4 preparations). This suggests that the loss of premotor GABAergic activity we observed could work to promote motor output at colder temperatures, which works adaptively for the animal when emerging from hibernation. NIH R01NS114514 (JS). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

ELECTRICAL ACTIVITY OF THE MUSCLES OF THE LOWER LIMBS OF KARATEKAS DURING THE PERFORMANCE OF A FRONT KICK

Subject. The study was aimed at analyzing the processes of muscles activation of Kyokushin karate practicioners during the kick performance. The process of skeletal muscle activation was studied by the analysis of their electrical activity. Our study aimed at the examination of the electrical activity of the muscles of the lower extremities of karate athletes during kick performance. Methods. The study involved 3 highly qualified karatekas (I Dan), aged 18-21 years, with a training experience of 12-15 years. Surface electromyogram (sEMG) was recorded during the Mae geri performance from Zenkutsu dachi stance for the following muscles: m. gluteus maximus, m. rectus femoris, m. biceps femoris, m. semitendinosus, m. gasterocnemius (caput lateralis), m. tibialis anterior. The activity period (AP, ms), mean amplitude (MA, % from maximal), and mean frequency (MF, % from maximal) were determined by sEMG analysis. Results. It was found that the duration of AP of different muscles ranges from 0.19 to 2.02 s during a Mae geri kick performance. The shortest AP was found for the m. gluteus maximus and m. rectus femoris. The highest MA values were registered for the m. tibialis anterior sinister (55%) and m. gasterocnemius dexter (47%), MF - for the anterior tibialis muscles (41-56%), right m. gasterocnemius (caput lateralis) (52%), and the m. rectus femoris dexter (47%). In many cases, the AP, MA, and MF of the supporting leg muscles exceeded those of the symmetrical muscles of a kicking leg. For many muscles, including the m. gluteus maximus, m. rectus femoris, and m. biceps femoris, the increase in MF of sEMG during kick significantly exceeds the MA changes. Conclusions. The main features of the activation of the muscles of the kicking and supporting leg of karate practitioners during the performance of the Mae geri kick were revealed. Most probably, one of the important mechanisms of muscles activation during the kick is the increase in the firing rate of motoneurons.

Investigation of Selective Innervation of Extraocular Muscle Compartments.

Recent magnetic resonance imaging studies have suggested that extraocular muscles (EOM) are further divided into transverse compartments that behave differentially and often unexpectedly during eye movements. Selective innervation of EOM compartments may explain the observation that certain horizontal recti compartments contribute to specific vertical eye movements and that some cyclovertical EOM compartments do not contribute to vertical vergence. We investigated the discharge characteristics of extraocular motoneurons during these eye movement tasks where EOM compartments behaved differentially for evidence of selective innervation. We recorded from all six extraocular motoneuron populations in the abducens, oculomotor, and trochlear nuclei as two non-human primates performed vertical vergence and vertical smooth-pursuit. The relationship between motoneuron firing rate, horizontal and vertical eye parameters of the innervated eye during each task was determined using multiple linear regression. All 26 medial rectus motoneurons recorded showed no significant modulation during vertical smooth-pursuit and vertical vergence. Twenty-eight of 30 abducens motoneurons showed no significant modulation during vertical vergence, and all 30 cells did not modulate during vertical smooth-pursuit. For the cyclovertical motoneurons, 147 of the 149 cells (44/46 inferior rectus, 27/27 superior oblique, 41/41 superior rectus and 35/35 inferior oblique) modulated significantly during vertical vergence. Extraocular motoneuron activity during vertical vergence and vertical smooth-pursuit does not support the theory that EOM compartments are selectively innervated. The observed differential behavior of EOM compartments is likely not driven by oculomotor control and could be due to passive change in EOM cross-sectional area.

Wrestle while you learn: EMG as a teaching tool for undergraduate skeletal muscle physiology teaching.

Wrestle while you learn: EMG as a teaching tool for undergraduate skeletal muscle physiology teaching.

The effects of model composition design choices on high-fidelity simulations of motoneuron recruitment and firing behaviors

Objective. Computational models often require tradeoffs, such as balancing detail with efficiency; yet optimal balance should incorporate sound design features that do not bias the results of the specific scientific question under investigation. The present study examines how model design choices impact simulation results. Approach. We developed a rigorously-validated high-fidelity computational model of the spinal motoneuron pool to study three long-standing model design practices which have yet to be examined for their impact on motoneuron recruitment, firing rate, and force simulations. The practices examined were the use of: (1) generic cell models to simulate different motoneuron types, (2) discrete property ranges for different motoneuron types, and (3) biological homogeneity of cell properties within motoneuron types. Main results. Our results show that each of these practices accentuates conditions of motoneuron recruitment based on the size principle, and minimizes conditions of mixed and reversed recruitment orders, which have been observed in animal and human recordings. Specifically, strict motoneuron orderly size recruitment occurs, but in a compressed range, after which mixed and reverse motoneuron recruitment occurs due to the overlap in electrical properties of different motoneuron types. Additionally, these practices underestimate the motoneuron firing rates and force data simulated by existing models. Significance. Our results indicate that current modeling practices increase conditions of motoneuron recruitment based on the size principle, and decrease conditions of mixed and reversed recruitment order, which, in turn, impacts the predictions made by existing models on motoneuron recruitment, firing rate, and force. Additionally, mixed and reverse motoneuron recruitment generated higher muscle force than orderly size motoneuron recruitment in these simulations and represents one potential scheme to increase muscle efficiency. The examined model design practices, as well as the present results, are applicable to neuronal modeling throughout the nervous system.

Synaptic loss and firing alterations in Axotomized Motoneurons are restored by vascular endothelial growth factor (VEGF) and VEGF-B

Vascular endothelial growth factor (VEGF), also known as VEGF-A, was discovered due to its vasculogenic and angiogenic activity, but a neuroprotective role for VEGF was later proven for lesions and disorders. In different models of motoneuronal degeneration, VEGF administration leads to a significant reduction of motoneuronal death. However, there is no information about the physiological state of spared motoneurons. We examined the trophic role of VEGF on axotomized motoneurons with recordings in alert animals using the oculomotor system as the experimental model, complemented with a synaptic study at the confocal microscopy level. Axotomy leads to drastic alterations in the discharge characteristics of abducens motoneurons, as well as to a substantial loss of their synaptic inputs. Retrograde delivery of VEGF completely restored the discharge activity and synaptically-driven signals in injured motoneurons, as demonstrated by correlating motoneuronal firing rate with motor performance. Moreover, VEGF-treated motoneurons recovered a normal density of synaptic boutons around motoneuronal somata and in the neuropil, in contrast to the low levels of synaptic terminals found after axotomy. VEGF also reduced the astrogliosis induced by axotomy in the abducens nucleus to control values. The administration of VEGF-B produced results similar to those of VEGF. This is the first work demonstrating that VEGF and VEGF-B restore the normal operating mode and synaptic inputs on injured motoneurons. Altogether these data indicate that these molecules are relevant synaptotrophic factors for motoneurons and support their clinical potential for the treatment of motoneuronal disorders.

Adaptations of motoneuron properties after weight-lifting training in rats.

Resistance training, with repeated short-term and high-intensity exercises, is responsible for an increase in muscle mass and force. The aim of this study was to determine whether such training induces adaptations in the electrophysiological properties of motoneurons innervating the trained muscles and to relate these adaptive changes to previous observations made on motor unit contractile properties. The study was performed on adult male Wistar rats. Animals from the training group were subjected to a 5-wk voluntary progressive weight-lifting program, whereas control rats were restricted to standard cage activity. Intracellular recordings from lumbar spinal motoneurons were made under pentobarbital anesthesia. Membrane properties were measured, and rhythmic firing of motoneurons was analyzed. Strength training evoked adaptive changes in both slow- and fast-type motoneurons, indicating their increased excitability. A shorter spike duration, a higher input resistance, a lower rheobase, a decrease in the minimum current required to evoke rhythmic firing, an increase in the maximum frequencies of the early-state firing (ESF) and the steady-state firing (SSF), and an increase in the respective slopes of the frequency-current (f/I) relationship were observed in fast motoneurons of the trained group. The increase in the maximum ESF and SSF frequencies and an increase in the SSF f/I slope were also present in slow motoneurons. Higher maximum firing rates of motoneurons as well as higher discharge frequencies evoked at the same level of intracellular depolarization current imply higher levels of tetanic forces developed by motor units over the operating range of force production after strength training.NEW & NOTEWORTHY Neuronal responses to weight-lifting training can be observed in altered properties of both slow and fast motoneurons. Motoneurons of trained animals are more excitable, require lower intracellular currents to evoke rhythmic firing, and have the ability to evoke higher maximum discharge frequencies during repetitive firing.

PICs in motoneurons do not scale with the size of the animal: a possible mechanism for faster speed of muscle contraction in smaller species

The majority of studies on the electrical properties of neurons are carried out in rodents, and in particular in mice. However, the minute size of this animal compared with humans potentially limits the relevance of the resulting insights. To be able to extrapolate results obtained in a small animal such as a rodent, one needs to have proper knowledge of the rules governing how electrical properties of neurons scale with the size of the animal. Generally speaking, electrical resistances of neurons increase as cell size decreases, and thus maintenance of equal depolarization across cells of different sizes requires the underlying currents to decrease in proportion to the size decrease. Thus it would generally be expected that voltage-sensitive currents are smaller in smaller animals. In this study, we used in vivo preparations to record electrical properties of spinal motoneurons in deeply anesthetized adult mice and cats. We found that PICs do not scale with size, but instead are constant in their amplitudes across these species. This constancy, coupled with the threefold differences in electrical resistances, means that PICs contribute a threefold larger depolarization in the mouse than in the cat. As a consequence, motoneuronal firing rate sharply increases as animal size decreases. These differences in firing rates are likely essential in allowing different species to control muscles with widely different contraction speeds (smaller animals have faster muscle fibers). Thus from our results we have identified a possible new mechanism for how electrical properties are tuned to match mechanical properties within the motor output system.NEW & NOTEWORTHY The small size of the mouse warrants concern over whether the properties of their neurons are a scaled version of those in larger animals or instead have unique features. Comparison of spinal motoneurons in mice to cats showed unique features. Firing rates in the mouse were much higher, in large part due to relatively larger persistent inward currents. These differences likely reflect adaptations for controlling much faster muscle fibers in mouse than cat.

Muscle fatigue increases beta-band coherence between the firing times of simultaneously active motor units in the first dorsal interosseous muscle.

Synchronization between the firing times of simultaneously active motor units (MUs) is generally assumed to increase during fatiguing contractions. To date, however, estimates of MU synchronization have relied on indirect measures, derived from surface electromyographic (EMG) interference signals. This study used intramuscular coherence to investigate the correlation between MU discharges in the first dorsal interosseous muscle during and immediately following a submaximal fatiguing contraction, and after rest. Coherence between composite MU spike trains, derived from decomposed surface EMG, were examined in the delta (1-4 Hz), alpha (8-12 Hz), beta (15-30 Hz), and gamma (30-60 Hz) frequency band ranges. A significant increase in MU coherence was observed in the delta, alpha, and beta frequency bands postfatigue. In addition, wavelet coherence revealed a tendency for delta-, alpha-, and beta-band coherence to increase during the fatiguing contraction, with subjects exhibiting low initial coherence values displaying the greatest relative increase. This was accompanied by an increase in MU short-term synchronization and a decline in mean firing rate of the majority of MUs detected during the sustained contraction. A model of the motoneuron pool and surface EMG was used to investigate factors influencing the coherence estimate. Simulation results indicated that changes in motoneuron inhibition and firing rates alone could not directly account for increased beta-band coherence postfatigue. The observed increase is, therefore, more likely to arise from an increase in the strength of correlated inputs to MUs as the muscle fatigues.

Current injection and receptor-mediated excitation produce similar maximal firing rates in hypoglossal motoneurons.

The maximum firing rates of motoneurons (MNs), activated in response to synaptic drive, appear to be much lower than that elicited by current injection. It could be that the decrease in input resistance associated with increased synaptic activity (but not current injection) might blunt overall changes in membrane depolarization and thereby limit spike-frequency output. To test this idea, we recorded, in the same cells, maximal firing responses to current injection and to synaptic activation. We prepared 300 μm medullary slices in neonatal rats that contained hypoglossal MNs and used whole-cell patch-clamp electrophysiology to record their maximum firing rates in response to triangular-ramp current injections and to glutamate receptor-mediated excitation. Brief pressure pulses of high-concentration glutamate led to significant depolarization, high firing rates, and temporary cessation of spiking due to spike inactivation. In the same cells, we applied current clamp protocols that approximated the time course of membrane potential change associated with glutamate application and with peak current levels large enough to cause spike inactivation. Means (SD) of maximum firing rates obtained in response to glutamate application were nearly identical to those obtained in response to ramp current injection [glutamate 47.1 ± 12.0 impulses (imp)/s, current injection 47.5 ± 11.2 imp/s], even though input resistance was 40% less during glutamate application compared with current injection. Therefore, these data suggest that the reduction in input resistance associated with receptor-mediated excitation does not, by itself, limit the maximal firing rate responses in MNs.

Cortical Spiking Network Interfaced with Virtual Musculoskeletal Arm and Robotic Arm.

Embedding computational models in the physical world is a critical step towards constraining their behavior and building practical applications. Here we aim to drive a realistic musculoskeletal arm model using a biomimetic cortical spiking model, and make a robot arm reproduce the same trajectories in real time. Our cortical model consisted of a 3-layered cortex, composed of several hundred spiking model-neurons, which display physiologically realistic dynamics. We interconnected the cortical model to a two-joint musculoskeletal model of a human arm, with realistic anatomical and biomechanical properties. The virtual arm received muscle excitations from the neuronal model, and fed back proprioceptive information, forming a closed-loop system. The cortical model was trained using spike timing-dependent reinforcement learning to drive the virtual arm in a 2D reaching task. Limb position was used to simultaneously control a robot arm using an improved network interface. Virtual arm muscle activations responded to motoneuron firing rates, with virtual arm muscles lengths encoded via population coding in the proprioceptive population. After training, the virtual arm performed reaching movements which were smoother and more realistic than those obtained using a simplistic arm model. This system provided access to both spiking network properties and to arm biophysical properties, including muscle forces. The use of a musculoskeletal virtual arm and the improved control system allowed the robot arm to perform movements which were smoother than those reported in our previous paper using a simplistic arm. This work provides a novel approach consisting of bidirectionally connecting a cortical model to a realistic virtual arm, and using the system output to drive a robotic arm in real time. Our techniques are applicable to the future development of brain neuroprosthetic control systems, and may enable enhanced brain-machine interfaces with the possibility for finer control of limb prosthetics.

Physiological consequences of doublet discharges on motoneuronal firing and motor unit force.

The double discharges are observed at the onset of contractions of mammalian motor units (MUs), especially during their recruitment to strong or fast movements. Doublets lead to MU force increase and improve ability of muscles to maintain high force during prolonged contractions. In this review we discuss an ability to produce doublets by fast and slow motoneurons (MNs), their influence on the course of action potential afterhyperpolarization (AHP) as well as its role in modulation of the initial stage of the firing pattern of MNs. In conclusion, a generation of doublets is an important strategy of motor control, responsible for fitting the motoneuronal firing rate to the optimal for MUs at the start of their contraction, necessary for increment of muscle force.

Swimming against the tide: investigations of the C-bouton synapse.

C-boutons are important cholinergic modulatory loci for state-dependent alterations in motoneuron firing rate. m2 receptors are concentrated postsynaptic to C-boutons, and m2 receptor activation increases motoneuron excitability by reducing the action potential afterhyperpolarization. Here, using an intensive review of the current literature as well as data from our laboratory, we illustrate that C-bouton postsynaptic sites comprise a unique structural/functional domain containing appropriate cellular machinery (a “signaling ensemble”) for cholinergic regulation of outward K+ currents. Moreover, synaptic reorganization at these critical sites has been observed in a variety of pathologic states. Yet despite recent advances, there are still great challenges for understanding the role of C-bouton regulation and dysregulation in human health and disease. The development of new therapeutic interventions for devastating neurological conditions will rely on a complete understanding of the molecular mechanisms that underlie these complex synapses. Therefore, to close this review, we propose a comprehensive hypothetical mechanism for the cholinergic modification of α-MN excitability at C-bouton synapses, based on findings in several well-characterized neuronal systems.

Changes in motoneuron afterhyperpolarization duration in stroke survivors.

Hemispheric brain injury resulting from a stroke is often accompanied by muscle weakness in limbs contralateral to the lesion. In the present study, we investigated whether weakness in contralesional hand muscle in stroke survivors is partially attributable to alterations in motor unit activation, including alterations in firing rate modulation range. The afterhyperpolarization (AHP) potential of a motoneuron is a primary determinant of motoneuron firing rate. We examined differences in AHP duration in motoneurons innervating paretic and less impaired (contralateral) limb muscles of hemiparetic stroke survivors as well as in control subjects. A novel surface EMG (sEMG) electrode was used to record motor units from the first dorsal interosseous muscle. The sEMG data were subsequently decomposed to derive single-motor unit events, which were then utilized to produce interval (ISI) histograms of the motoneuron discharges. A modified version of interval death rate (IDR) analysis was used to estimate AHP duration. Results from data analyses performed on both arms of 11 stroke subjects and in 7 age-matched control subjects suggest that AHP duration is significantly longer for motor units innervating paretic muscle compared with units in contralateral muscles and in units of intact subjects. These results were supported by a coefficient of variation (CV) analysis showing that paretic motor unit discharges have a lower CV than either contralateral or control units. This study suggests that after stroke biophysical changes occur at the motoneuron level, potentially contributing to lower firing rates and potentially leading to less efficient force production in paretic muscles.

Matchmaking: SK channels, C‐boutons and motor units

Matchmaking: SK channels, C‐boutons and motor units

Glutamate modulates the firing rate in oculomotor nucleus motoneurons as a function of the recruitment threshold current

Studies in alert preparations have demonstrated that ocular motoneurons exhibit a phasic–tonic firing rate related to eye velocity and position, respectively. The slopes of these relationships are higher in motoneurons with higher recruitment threshold and have been proposed to depend upon synaptic input. To investigate this hypothesis, motoneurons of the rat oculomotor nucleus were recorded in a brain slice preparation in control conditions and during glutamate (5 μm) application to the bath. Glutamate did not affect membrane potential or input resistance, but produced a decrease in rheobase and depolarization voltage as a function of the current needed for generating a maintained repetitive discharge (recruitment threshold current). In addition, glutamate compressed the range of recruitment threshold current (0.1–0.4 nA) as compared to the control (0.15–0.7 nA). Glutamate exposed motoneurons showed an increase in the tonic frequency gain and the peak frequency. Such increments depended on the recruitment threshold current and the last recruited motoneurons almost doubled the tonic frequency gain (35.2 vs. 57.9 spikes s(−1) nA(−1)) and the peak frequency (52.4 vs. 102.6 spikes s(−1)). Finally, glutamate increased the spike frequency adaptation due to a significant increase in the phasic firing component as compared to the tonic one. In conclusion, glutamate modulates tonic and phasic discharge properties as a function of the recruitment threshold current and, presumably, motoneuron size. These findings contribute to understand the link between cellular functions and motoneuron discharge during oculomotor behaviour.

Frequency-dependent amplification of stretch-evoked excitatory input in spinal motoneurons.

Voltage-dependent calcium and sodium channels mediating persistent inward currents (PICs) amplify the effects of synaptic inputs on the membrane potential and firing rate of motoneurons. CaPIC channels are thought to be relatively slow, whereas the NaPIC channels have fast kinetics. These different characteristics influence how synaptic inputs with different frequency content are amplified; the slow kinetics of Ca channels suggest that they can only contribute to amplification of low frequency inputs (<5 Hz). To characterize frequency-dependent amplification of excitatory postsynaptic potentials (EPSPs), we measured the averaged stretch-evoked EPSPs in cat medial gastrocnemius motoneurons in decerebrate cats at different subthreshold levels of membrane potential. EPSPs were produced by muscle spindle afferents activated by stretching the homonymous and synergist muscles at frequencies of 5-50 Hz. We adjusted the stretch amplitudes at different frequencies to produce approximately the same peak-to-peak EPSP amplitude and quantified the amount of amplification by expressing the EPSP integral at different levels of depolarization as a percentage of that measured with the membrane hyperpolarized. Amplification was observed at all stretch frequencies but generally decreased with increasing stretch frequency. However, in many cells the amount of amplification was greater at 10 Hz than at 5 Hz. Fast amplification was generally reduced or absent when the lidocaine derivative QX-314 was included in the electrode solution, supporting a strong contribution from Na channels. These results suggest that NaPICs can combine with CaPICs to enhance motoneuron responses to modulations of synaptic drive over a physiologically significant range of frequencies.

Increased pentobarbital insensitivity in hypoglossal (XII) motoneurons during late pregnancy is consistent with increased epsilon subunit expression in GABAA receptors (GABAARs)

Progesterone and allopregnanolone (ALLO) are increased centrally during late pregnancy. Increased ALLO creates a risk for excessive neuronal inhibition because ALLO is a positive allosteric modulator of GABAARs. We hypothesized that XII motoneurons compensate for increased inhibition during late pregnancy by increasing epsilon subunit expression in GABAARs because the epsilon subunit confers insensitivity to positive allosteric modulators, such as ALLO and pentobarbital. To test this question, medullary slices were taken from G18 pregnant rats (n=7), adult male (n=5), and adult female (n=2) rats. Extracellular multichannel electrodes recorded spontaneous action potentials in XII motoneurons. To pharmacologically test for epsilon subunits, slices were sequentially exposed to 200 and 300 μM pentobarbital (45 min each). During the last 15 min of 300 μM pentobarbital, XII motoneuron firing rates steadily decreased to 37±9% (n=105 cells) and 36±5% (n=32 cells) of baseline in slices from male and female rats, respectively. In contrast, XII motoneuron firing rates from G18 rat slices increased to 120±29% of baseline (n=78 cells). These data show that pregnancy caused XII motoneurons to become more resistant to positive allosteric modulation by pentobarbital. We speculate that increased epsilon expression prevents excessive ALLO‐dependent inhibition during pregnancy. Supported by NIH T32 HL07654.

Corrigendum

CorrigendumCorrigendumPublished Online:01 Mar 2012https://doi.org/10.1152/jn.z9k-1251-corr.2011Original articleMoreSectionsPDF (69 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat Volume 104, August 2010De Luca CJ and Hostage EC. Relationship between firing rate and recruitment threshold of motoneurons in voluntary isometric contractions. J Neurophysiol 104: , 2010; doi:10.1152/jn.01018.2009; http://jn.physiology.org/content/104/2/1034.full.Incorrect values appear in Table 3 for parameters A and C. The correct values are A = 116, C = −21 for the vastus lateralis (VL) muscle; A = 85, C = −23 for the first dorsal interosseous (FDI) muscle; A = 65, C = −15 for the tibialis anterior (TA) muscle.Also, Fig. 7 erroneously reports the projected firing rate and firing rate velocity for the FDI muscle, not for the VL muscle as indicated. Figure 7 should thus be replaced by the following figure relating to the VL muscle. Note that the curves presented in Fig. 7 are derived using experimental data recorded between 20 and 100% MVC (0.2 to 1 normalized to MVC). Thus, the curves presented in Fig. 7 are not necessarily an accurate representation of the firing rate behavior below 20% MVC.Fig. 7.A: projected firing rates of motor units in the VL muscle calculated from Eq. 4. The firing rates of motor units recruited between 10 and 90% MVC at intervals of 10% MVC are shown. The curves are limited to this range because the empirical data were so limited. B: projected velocity of the firing rates of motor units in the VL muscle calculated from Eq. 5. The firing rates of motor units recruited between 10 and 90% MVC at intervals of 10% MVC are shown. The curves are limited to this range because the empirical data were so limited.Download figureDownload PowerPointThis article has no references to display. Download PDF Previous Back to Top FiguresReferencesRelatedInformationRelated ArticlesRelationship Between Firing Rate and Recruitment Threshold of Motoneurons in Voluntary Isometric Contractions 01 Aug 2010Journal of Neurophysiology More from this issue > Volume 107Issue 5March 2012Pages 1544-1544 Copyright & PermissionsCopyright © 2012 the American Physiological Societyhttps://doi.org/10.1152/jn.z9k-1251-corr.2011History Published online 1 March 2012 Published in print 1 March 2012 Metrics