Maximum Firing Rate Research Articles

Relationships between voluntary activation and motor unit firing rate during maximal voluntary contractions in young and older adults

The extent to which an individual can voluntarily produce maximal muscular force can be estimated using the interpolated twitch technique. Incompleteness of activation is typically attributed to either incomplete recruitment, suboptimal firing rates or both of these mechanisms. The purpose of this study was to assess the relationship between muscle activation and maximal motor unit firing rates. Measures of muscle activation and motor unit firing rates during maximal effort contractions were obtained from 15 subjects (8 young, 7 older) throughout a 6-week strength training program for the knee extensors. High resolution interpolated twitch responses were obtained using a circuit that removes the force level of the maximal voluntary contraction prior to amplification of the additional evoked force. Maximal firing rates were obtained using a four-wire needle electrode. Electrical stimulation of the knee extensors during maximal effort contractions evoked a transient increase in the force and the amplitude of this additional force was correlated with maximal firing rates at r = -0.62 (p < 0.05). Central activation ratio and activation level, two indexes of activation, were correlated with maximal firing rates at r = 0.58 (p < 0.05) and r = 0.68 (p < 0.05), respectively. The training program elicited parallel increases in muscular activation and maximal firing rates. These results provide direct support for maximal firing rate as a significant factor limiting maximal force production.

The medial nucleus of the trapezoid body in rat: spectral and temporal properties vary with anatomical location of the units

The medial nucleus of the trapezoid body (MNTB) is a distinct nucleus in the superior olivary complex that transforms excitatory input from the cochlear nucleus into a widespread inhibitory output to distinct auditory brainstem nuclei. Few studies have dealt with the response properties of MNTB neurons to sound stimulation using in vivo preparations. In order to have a better understanding of the functional significance of the MNTB in auditory processing we report the basic temporal and spectral response properties of its principal cells using single-unit extracellular recordings to acoustic stimulation with pure tones and amplitude-modulated stimuli in the rat. Ninety-seven per cent of units showed V-shaped frequency response areas. Rate level functions were mainly saturating (51%) or monotonic (45%) at high intensities. Post-stimulus time histograms typically were characterised as primary-like with notch (59%) or primary-like (33%). Units showed good phase-locking to sinusoidally amplitude-modulated signals with vector strength VS values up to 0.87. Modulation transfer functions had low-pass shapes at near-threshold levels, with cut-off frequencies ranging from 370 to 1270 Hz. Exploration of the relationship between the temporal and spectral properties and the location of the units in the MNTB yielded characteristic frequency (CF)-dependent response properties (latency, Q(10) and cut-off frequency) following a medio-lateral gradient, and CF-independent response features (maximum firing rate) following a dorso-ventral gradient.

Functional Trade-Offs in White Matter Axonal Scaling

The brains of large mammals have lower rates of metabolism than those of small mammals, but the functional consequences of this scaling are not well understood. An attractive target for analysis is axons, whose size, speed and energy consumption are straightforwardly related. Here we show that from shrews to whales, the composition of white matter shifts from compact, slow-conducting, and energetically expensive unmyelinated axons to large, fast-conducting, and energetically inexpensive myelinated axons. The fastest axons have conduction times of 1-5 ms across the neocortex and <1 ms from the eye to the brain, suggesting that in select sets of communicating fibers, large brains reduce transmission delays and metabolic firing costs at the expense of increased volume. Delays and potential imprecision in cross-brain conduction times are especially great in unmyelinated axons, which may transmit information via firing rate rather than precise spike timing. In neocortex, axon size distributions can account for the scaling of per-volume metabolic rate and suggest a maximum supportable firing rate, averaged across all axons, of 7 +/- 2 Hz. Axon size distributions also account for the scaling of white matter volume with respect to brain size. The heterogeneous white matter composition found in large brains thus reflects a metabolically constrained trade-off that reduces both volume and conduction time.

Who needs A current? Functional remodelling in the Kv4.2−/− mouse

Who needs A current? Functional remodelling in the Kv4.2−/− mouse

How Optimal Stimuli for Sensory Neurons Are Constrained by Network Architecture

Identifying the optimal stimuli for a sensory neuron is often a difficult process involving trial and error. By analyzing the relationship between stimuli and responses in feedforward and stable recurrent neural network models, we find that the stimulus yielding the maximum firing rate response always lies on the topological boundary of the collection of all allowable stimuli, provided that individual neurons have increasing input-output relations or gain functions and that the synaptic connections are convergent between layers with nondegenerate weight matrices. This result suggests that in neurophysiological experiments under these conditions, only stimuli on the boundary need to be tested in order to maximize the response, thereby potentially reducing the number of trials needed for finding the most effective stimuli. Even when the gain functions allow firing rate cutoff or saturation, a peak still cannot exist in the stimulus-response relation in the sense that moving away from the optimum stimulus always reduces the response. We further demonstrate that the condition for nondegenerate synaptic connections also implies that proper stimuli can independently perturb the activities of all neurons in the same layer. One example of this type of manipulation is changing the activity of a single neuron in a given processing layer while keeping that of all others constant. Such stimulus perturbations might help experimentally isolate the interactions of selected neurons within a network.

Coding of distributed, topographic and non-specific representations within the brain

This article explores the theoretical basis of coding within topographic representations, where neurons encoding specific features such as locations, are arranged into maps. A novel type of representation, termed non-specific, where each neuron does not encode specific features is also postulated. In common with the previously described distributed representations [Rolls, E.T., Treves, A., 1998. Neural Networks and Brain Function. Oxford University Press, Oxford], topographic representations display an exponential relationship between stimuli encoded and both number of neurons and maximum firing rate of those neurons. The non-specific representations described here display a binomial expansion between the number of stimuli encoded and the sum of the number of neurons and the maximum firing rate; therefore groups of non-specific neurons usually encode less stimuli than equivalent topographic layers of neurons. Lower and higher order sensory regions of the brain use either topographic or distributed representations to encode information. It is proposed that non-specific representations may occur in regions of the brain where different types of information may be represented by the same neurons, as occurs in the prefrontal cortex.

Differential regulation of action potential firing in adult murine thalamocortical neurons by Kv3.2, Kv1, and SK potassium and N‐type calcium channels

Sensory signals of widely differing dynamic range and intensity are transformed into a common firing rate code by thalamocortical neurons. While a great deal is known about the ionic currents, far less is known about the specific channel subtypes regulating thalamic firing rates. We hypothesized that different K(+) and Ca(2+) channel subtypes control different stimulus-response curve properties. To define the channels, we measured firing rate while pharmacologically or genetically modulating specific channel subtypes. Inhibiting Kv3.2 K(+) channels strongly suppressed maximum firing rate by impairing membrane potential repolarization, while playing no role in the firing response to threshold stimuli. By contrast, inhibiting Kv1 channels with alpha-dendrotoxin or maurotoxin strongly increased firing rates to threshold stimuli by reducing the membrane potential where action potentials fire (V(th)). Inhibiting SK Ca(2+)-activated K(+) channels with apamin robustly increased gain (slope of the stimulus-response curve) and maximum firing rate, with minimum effects on threshold responses. Inhibiting N-type Ca(2+) channels with omega-conotoxin GVIA or omega-conotoxin MVIIC partially mimicked apamin, while inhibiting L-type and P/Q-type Ca(2+) channels had small or no effects. EPSC-like current injections closely mimicked the results from tonic currents. Our results show that Kv3.2, Kv1, SK potassium and N-type calcium channels strongly regulate thalamic relay neuron sensory transmission and that each channel subtype controls a different stimulus-response curve property. Differential regulation of threshold, gain and maximum firing rate may help vary the stimulus-response properties across and within thalamic nuclei, normalize responses to diverse sensory inputs, and underlie sensory perception disorders.

Neurons Skip a Beat during Fast Ripples

Fast ripples are EEG transients emanating from epileptic foci, but fast-ripple frequencies far exceed maximal neuronal firing rates. In this issue of Neuron, Menendez de la Prida and coworkers propose that out-of-phase firing of a subpopulation of neurons during physiological ripple activity effectively doubles the ripple frequency to produce fast ripples.

Rate and timing dependent plasticity in a biophysical model of synaptic plasticity

Activity dependent synaptic plasticity is typically induced by delivering a large number (~1000) of highly regular electrical stimuli, designed to saturate the synaptic strengths. However, natural spike trains typically contain a small number of spikes with variable regularity. We investigate how spike patterns with physiologically realistic spike counts generate plasticity using a standard, biophysical model of calcium-dependent plasticity. We find that for physiological spike patterns, there exists a resonant frequency (fmax) that induces maximal firing rate dependent potentiation and periodic stimuli produce substantially more plasticity than aperiodic ones. Frequency dependent facilitation (depression) of the synapses does not affect the fmax but increases (decreases) the amount of plasticity; relative change in the amount of plasticity varies with number of spikes. The model combines the rate dependent plasticity with spike timing dependent plasticity (STDP) and shows that the direction of STDP depends both on the number of postsynaptic spikes that a single presynaptic spike is paired with and on the frequency of postsynaptic discharge. We discuss experimental tests of these results, and their functional significance for learning under natural, dynamical conditions.

Automatic spike detection based on adaptive template matching for extracellular neural recordings

Recordings of extracellular neural activity are used in many clinical applications and scientific studies. In most cases, these signals are analyzed as a point process, and a spike detection algorithm is required to estimate the times at which action potentials occurred. Recordings from high-density microelectrode arrays (MEAs) and low-impedance microelectrodes often have a low signal-to-noise ratio (SNR < 10) and contain action potentials from more than one neuron. We describe a new detection algorithm based on template matching that only requires the user to specify the minimum and maximum firing rates of the neurons. The algorithm iteratively estimates the morphology of the most prominent action potentials. It is able to achieve a sensitivity of >90% with a false positive rate of <5 Hz in recordings with an estimated SNR = 3, and it performs better than an optimal threshold detector in recordings with an estimated SNR > 2.5.

Spike-rate adaptation and neuronal bursting in a mean-field model of brain activity

Spike-rate adaptation is investigated within a mean-field model of brain activity. Two different mechanisms of negative feedback are considered; one involving modulation of the mean firing threshold, and the other, modulation of the mean synaptic strength. Adaptation to a constant stimulus is shown to take place for both mechanisms, and limit-cycle oscillations in the firing rate corresponding to bursts of neuronal activity are investigated. These oscillations are found to result from a Hopf bifurcation when the equilibrium lies between the local maximum and local minimum of a given nullcline. Oscillations with amplitudes significantly below the maximum firing rate are found over a narrow range of possible equilibriums.

Transgenic Mouse Lines Subdivide Medial Vestibular Nucleus Neurons into Discrete, Neurochemically Distinct Populations

The identification of neuron types within circuits is fundamental to understanding their relevance to behavior. In the vestibular nuclei, several classes of neurons have been defined in vivo on the basis of their activity during behavior, but it is unclear how those types correspond to neurons identified in slice preparations. By targeting recordings to neurons labeled in transgenic mouse lines, this study reveals that the continuous distribution of intrinsic parameters observed in medial vestibular nucleus (MVN) neurons can be neatly subdivided into two populations of neurons, one of which is GABAergic and the other of which is exclusively glycinergic or glutamatergic. In slice recordings, GABAergic neurons labeled in the EGFP (enhanced green fluorescent protein)-expressing inhibitory neuron (GIN) line displayed lower maximum firing rates (<250 Hz) than glycinergic and glutamatergic neurons labeled in the yellow fluorescent protein-16 (YFP-16) line (up to 500 Hz). In contrast to cortical and hippocampal interneurons, GABAergic MVN neurons exhibited wider action potentials than glutamatergic (and glycinergic) neurons. Responses to current injection differed between the neurons labeled in the two lines, with GIN neurons modulating their firing rates over a smaller input range, adapting less during steady depolarization, and exhibiting less rebound firing than YFP-16 neurons. These results provide a scheme for robust classification of unidentified MVN neurons by their physiological properties. Finally, dye labeling in slices shows that both GABAergic and glycinergic neurons project to the contralateral vestibular nuclei, indicating that commissural inhibition is accomplished through at least two processing streams with differential input and output properties.

Unitary IPSPs enhance hilar mossy cell gain in the rat hippocampus

Mechanisms that control neuronal gain allow for adaptive rescaling to synaptic inputs of varying strengths or frequencies. Here, we show that unitary IPSPs (uIPSPs) modulate gain and unitary EPSP (uEPSP)-action potential coupling in mossy cells (MCs) from rat hippocampal slices. Mossy fibre-evoked uEPSCs were large, facilitated and were suppressed by the group II metabotropic glutamate agonist LY354740. Conversely, uIPSCs were smaller, depressed and were not affected by LY354740, but exerted strong inhibitory control over uEPSP-action potential coupling. The IPSC reversal potential was determined by gramicidin perforated patch recordings to be -65.3 +/- 5.0 mV, lying between the resting membrane potential (-75.3 +/- 1.1 mV) and the action potential threshold (-56.5 +/- 2.4 mV). When applied at theta frequency (10 Hz), uIPSPs increased the offset of the MC input-output response to depolarizing current injection, but also increased gain, maximal firing rate and the slope of the depolarization preceding action potentials. These effects were unchanged by the Ca2+ and HCN channel blockers mibefradil and ZD7288, respectively. The height and maximal slope of MC action potentials during tonic depolarization were also increased by uIPSPs, and the decay of uIPSP conductances injected by dynamic clamp at subthreshold membrane potentials was prolonged by TTX. Application of the muscarinic agonist pilocarpine mimicked the effect of IPSPs on MC maximal firing rate, and action potential height and slope, and this was reversed by the GABA(A) antagonist gabazine. Thus, uIPSPs can increase neuronal gain under hyperexcitable conditions, and this effect is probably due to the de-inactivation of a TTX-sensitive voltage-dependent Na+ conductance.

The Linear Computational Algorithm of Cerebellar Purkinje Cells

The orchestration of simple motor tasks by the cerebellum results in coordinated movement and the maintenance of balance. The cerebellum integrates sensory and cortical information to generate the signals required for the coordinated execution of simple motor tasks. These signals originate in the firing rate of Purkinje cells, each of which integrates sensory and cortical information conveyed by granule cell synaptic inputs. Given the importance of the granule cell input-Purkinje cell output function for cerebellar computation, this algorithm was determined. Using several stimulation paradigms, including those that mimicked patterns of granule cell activity similar to those observed in vivo, we quantified the poststimulus maximum firing rate and number of extra spikes in response to granule cell synaptic input. Both of these parameters linearly encoded the strength of synaptic input when inhibitory synaptic transmission was blocked. This linear algorithm was independent of the location or temporal pattern of synaptic input. With inhibitory synaptic transmission intact, the maximum firing rate, but not the number of extra spikes, encoded the strength of granule cell synaptic input. Furthermore, the maximum firing rate of Purkinje cells linearly encoded the strength of synaptic input whether or not the activation of granule cells resulted in a pause in Purkinje cell firing. On the basis of the data presented, we propose that Purkinje cells encode the strength of granule cell synaptic input in their maximum firing rate with a linear algorithm.

Impaired Motor Function in Mice With Cell-Specific Knockout of Sodium ChannelScn8a(NaV1.6) in Cerebellar Purkinje Neurons and Granule Cells

The Scn8a gene encodes the voltage-gated Na channel alpha subunit Na(V)1.6, which is widely expressed throughout the nervous system. Global null mutations that eliminate Scn8a in all cells result in severe motor dysfunction and premature death, precluding analysis of the physiological role of Na(V)1.6 in different neuronal types. To test the effect of cerebellar Na(V)1.6 on motor coordination in mice, we used the Cre-lox system to eliminate Scn8a expression exclusively in Purkinje neurons (Purkinje KO) and/or granule neurons (granule KO). Whereas granule KO mice had only minor behavioral defects, adult Purkinje KO mice exhibited ataxia, tremor, and impaired coordination. These disorders were exacerbated in double mutants lacking Scn8a in both Purkinje and granule cells (double KO). In Purkinje cells isolated from adult Purkinje KO and double KO but not granule KO mice, the ratio of resurgent-to-transient tetrodotoxin- (TTX)-sensitive Na current amplitudes decreased from approximately 15 to approximately 5%. In cerebellar slices, Purkinje cell spontaneous and maximal firing rates were reduced 10-fold and twofold relative to control in Purkinje KO and double KO but not granule KO mice. Additionally, short-term plasticity of high-frequency parallel fiber EPSCs was altered relative to control in Purkinje KO and double KO but not granule KO mice. These data suggest that the specialized kinetics of Purkinje Na channels depend directly on Scn8a expression. The loss of these channels leads to a decrease in Purkinje cell firing rates as well as a modification of the synaptic properties of afferent parallel fibers, with the ultimate consequence of disrupting motor behavior.

Doublet Discharges in Motoneurons of Young and Older Adults

The purpose of this study was to investigate the occurrence of motor unit doublet discharges in young and older individuals at different rates of increasing force. Participants included eight young (21.9 +/- 3.56 yr) and eight older (74.1 +/- 8.79 yr) individuals, with equal numbers of males and females in each group. Motor unit activity was recorded from the tibialis anterior during isometric dorsiflexion using a four-wire needle electrode. Subjects performed three ramp contractions from zero to 50% maximal voluntary contraction (MVC) force at each of three rates: 10, 30, and 50% MVC/s. Overall, the occurrence of doublets was significantly higher in the young than in the older individuals. However, neither group showed differences in the occurrence of doublets across the three rates of force production. Doublet firings were observed in 45.6 (young) and 35.1% (old) of motor units at 10% MVC/s; 48.6 (young) and 22.5% (old) of motor units at 30% MVC/s; and 48.4 (young) and 31.4% (old) at 50% MVC/s. The maximal firing rate was significantly higher and the force at which the motor units were recruited was significantly lower for those units that fired doublets than those that did not. The force at which doublets occurred ranged from 3.42 to 50% MVC in the young subjects and from 0 (force onset) to 50% MVC in the older subjects. The results of this study suggest that the occurrence of doublets is dependent on both motor unit firing rate and force level. The lower incidence of doublets in older individuals may be attributable to changes in the intrinsic properties of the motoneurons with aging, which appear to play a role in doublet discharges.

Reduction in maximal firing rate of motoneurons after 1-week immobilization of finger muscle in human subjects

We investigated the effects of immobilization on the maximal motoneuronal firing rate recorded from the first dorsal interosseous (FDI) during voluntary isometric contraction. In five human subjects, the middle finger, index finger, and thumb were immobilized for 1 week in a fiber-glass cast, which kept FDI in a shortened position. During a maximal voluntary contraction, single muscle-fiber action potentials were recorded using a tungsten microelectrode, and mean firing rate was calculated for each action-potential train. Three recording sessions were held: before immobilization (pre), after immobilization (post), and after a 1-week recovery period (recovery). The mean firing rate of FDI motoneurons during maximal voluntary contraction was decreased immediately after the 1-week immobilization (pre: 39.0 ± 3.2 Hz, number of detected spike trains ( n) = 353; post: 33.1 ± 1.5 Hz, n = 285; p < 0.05), and there was a return to control after the recovery period (40.2 ± 3.4 Hz, n = 236). This suggests that the maximal motoneuronal firing rate achieved during maximal voluntary contraction is reduced after short-term immobilization. The functional implications and the contribution of this phenomenon to the immobilization-induced reduction in maximal voluntary force are discussed.

Effects of Noise-Induced Hearing Loss at Young Age on Voice Onset Time and Gap-in-Noise Representations in Adult Cat Primary Auditory Cortex

Here we show that mild hearing loss induced by noise exposure in early age causes a decrease in neural temporal resolution when measured in adulthood. We investigated the effect of this chronic hearing loss on the representation of a voice onset time (VOT) and a gap-duration continuum in primary auditory cortex (AI) in cats, which were exposed at the age of 6 weeks to a 120-dB SPL, 5-kHz 1/3 octave noise band for 2 h. The resulting hearing loss measured using auditory brainstem responses and cortical multiunit thresholds at 4-6 months of age was 20-40 dB between 1 and 32 kHz. Multiple single-unit activity was recorded in seven noise-exposed cats and nine control cats related to the presentation of a/ba/-/pa/ continuum in which VOT was varied in 5-ms step from 0 to 70 ms. We also obtained data for noise bursts with gaps, of duration equal to the VOT, embedded in noise 5 ms after the onset. Both stimuli were presented at 65 dB SPL. Minimum VOT and early-gap duration were defined as the lowest value in which an on-response, significantly above the spontaneous activity, to both the leading and trailing noise bursts or vowel was obtained. The mild chronic noise-induced hearing loss increased the minimum detectable VOT and gap duration by 10 ms. We also analyzed the maximum firing rate (FRmax) and the latency of the responses as a function of VOT and gap duration and found a significant reduction in the FRmax to the trailing noise burst for gap durations above 50 ms. This suggests that mild hearing loss acquired in early age may affect cortical temporal processing in adulthood.

Maximal motor unit firing rates during isometric resistance training in men

This study measured changes in maximal voluntary contraction (MVC) force, percentage maximal activation, maximal surface EMG, M-wave amplitude and average motor unit firing rates during the initial 3 weeks of isometric resistance training of the quadriceps muscle. Ten men participated in a resistance training programme three times a week for 3 weeks and 10 men participated as a control group. In the training group, MVC increased by 35% (from 761 +/- 77 to 1031 +/- 78 N) by the end of the 3 weeks. There were no changes in mean motor unit firing rates during submaximal or maximal voluntary contractions of 50 (15.51 +/- 1.48 Hz), 75 (20.23 +/- 1.85 Hz) or 100% MVC (42.25 +/- 2.72 Hz) with isometric resistance training. There was also no change in maximal surface EMG relative to the M-wave amplitude. However, there was a small increase in maximal activation (from 95.7 +/- 1.83 to 98.44 +/- 0.66%) as measured by the twitch interpolation technique. There were no changes in any of the parameters measured in the control group. It is suggested that mechanisms other than increases in average motor unit firing rates contributed to the increase in maximal force output with resistance training. Such mechanisms may include a combination of increased motor unit recruitment, enhanced protein synthesis, and changes in motor unit synchronization and muscle activation patterns across the quadriceps synergy.

Computer simulations of high-pass filtering in zebrafish larval muscle fibres

Larval somatic muscle of the zebrafish, Danio rerio, like that of some other organisms, responds to a sustained depolarization with one, and only one, action potential. Here, we report computer simulations, using the NEURON simulation programme, of sodium and potassium currents of somatic muscle of larval Danio rerio to investigate their possible contribution to once-only firing. Our computer model incorporated simulated sodium and potassium ion channels based on steady-state and kinetic parameters derived from a recent electrophysiological study. The model responded to sustained depolarizations with a single action potential at all levels of depolarization above threshold. By varying several parameters of the sodium and potassium currents systematically, the minimum changes necessary to produce repetitive firing were found to be a positive shift in the half-inactivation and a negative shift in the half-activation potentials for the sodium current, accompanied by a slowing of the rate of inactivation to half of the experimentally observed values. This suggests that once-only spiking can be attributed to the steady-state values of activation and inactivation of the sodium current, along with a slower rate of inactivation. Mapping of the resultant firing properties against steady-state and kinetic ion channel parameters revealed a high safety factor for once-only firing and showed that the time constant of inactivation of the sodium current was the key determinant of once-only or repetitive firing. The rapidly inactivating potassium current does not influence once-only firing or the maximum rate of firing in response to periodic excitation in these simulations. Although a contribution of other currents to produce once-only firing has not been excluded, this model suggests that the properties of the sodium current are sufficient to account for once-only firing.