Firing Rate Relationship Research Articles

An examination of motor unit firing rates during steady torque of maximal efforts with either an explosive or slower rate of torque development.

What is the central question of this study? The aim was to explore agonist and antagonist motor unit firing rates during maximal efforts performed with either an explosive or a slower rate of torque development. What is the main finding and its importance? The antagonist muscle presented a motor unit firing rate relationship similar to the agonist muscle. Additionally, the motor units of both muscles exhibited higher firing rates during explosive maximal contractions than during maximal contractions performed at a slower rate of torque development. These results could prove useful to future research analysing the effects of age, disease, resistance training and/or fatigue-related alterations to motor unit firing rates. The primary purpose of the present study was to examine motor unit (MU) firing rates in agonist and antagonist muscles during periods of steady, maximal efforts using explosive and slower rates of torque development. A secondary purpose was to analyse the MU firing rate versus action potential amplitude relationships of the agonist and antagonist muscles during maximal efforts. Thirteen subjects (mean±SD; age, 21.2±3.6years; mass 81.1±21.3kg; and stature, 177.1±9.9cm) performed two maximal isometric trapezoid muscle actions of the elbow flexors that included either an explosive or a slower, linearly increasing rate (ramp) of torque development. Surface EMG signals of the biceps brachii (BB) and triceps brachii (TB) muscles were collected and decomposed into their constituent MU action potential trains. The MU firing rate versus action potential amplitude relationships of the BB (agonist) and TB (antagonist) muscles were analysed. Moderate to strong relationships (|r|≥0.65) were present for the explosive and ramp contractions in the agonist and antagonist muscles. Firing rates of smaller and larger MUs were higher during the explosive [mean±SD; agonist=18.1±6.9pulses per second (pps), antagonist=22.0±3.9pps] than the ramp (agonist=14.0±5.1pps, antagonist=18.3±4.4pps) contractions for the agonist (P=0.013) and antagonist muscles (P=0.007). The antagonist muscle exhibits a similar MU firing rate versus action potential amplitude relationship to the agonist muscle at maximal efforts. Future research should investigate the effects of short-term resistance training on antagonist firing rates and the involvement of peripheral feedback on firing rates during maximal efforts performed at various rates of torque development.

Acetylcholine-gated current translates wake neuronal firing rate information into a spike timing-based code in Non-REM sleep, stabilizing neural network dynamics during memory consolidation.

Sleep is critical for memory consolidation, although the exact mechanisms mediating this process are unknown. Combining reduced network models and analysis of in vivo recordings, we tested the hypothesis that neuromodulatory changes in acetylcholine (ACh) levels during non-rapid eye movement (NREM) sleep mediate stabilization of network-wide firing patterns, with temporal order of neurons’ firing dependent on their mean firing rate during wake. In both reduced models and in vivo recordings from mouse hippocampus, we find that the relative order of firing among neurons during NREM sleep reflects their relative firing rates during prior wake. Our modeling results show that this remapping of wake-associated, firing frequency-based representations is based on NREM-associated changes in neuronal excitability mediated by ACh-gated potassium current. We also show that learning-dependent reordering of sequential firing during NREM sleep, together with spike timing-dependent plasticity (STDP), reconfigures neuronal firing rates across the network. This rescaling of firing rates has been reported in multiple brain circuits across periods of sleep. Our model and experimental data both suggest that this effect is amplified in neural circuits following learning. Together our data suggest that sleep may bias neural networks from firing rate-based towards phase-based information encoding to consolidate memories.

Weakly correlated activity of pallidal neurons in behaving monkeys.

The basal ganglia play a crucial role in the control of voluntary movements. Neurons in both the external and internal segments of the globus pallidus, the connecting and output nuclei of the basal ganglia, respectively, change their firing rates in relation to movements. Firing rate changes of movement‐related neurons seem to convey signals for motor control. On the other hand, coincident spikes among neurons, that is, correlated activity, may also contribute to motor control. To address this issue, we first identified multiple pallidal neurons receiving inputs from the forelimb regions of the primary motor cortex and supplementary motor area, recorded neuronal activity of these neurons simultaneously, and analyzed their spike correlations while monkeys performed a hand‐reaching task. Most (79%) pallidal neurons exhibited task‐related firing rate changes, whereas only a small fraction (20%) showed significant but small and short correlated activity during the task performance. These results suggest that motor control signals are conveyed primarily by firing rate changes in the external and internal segments of the globus pallidus and that the contribution of correlated activity may play only a minor role in the healthy state.

Non-REM Sleep Facilitates Consolidation of Contextual Fear Memory Through Temporal Coding Among Hippocampal Neurons

Sleep plays a critical role in memory consolidation, although the exact mechanisms mediating this process are unknown. Combining computational and in vivo experimental approaches, we test the hypothesis that reduced cholinergic input to the hippocampus during non-rapid eye movement (NREM) sleep generates stable spike timing relationships between neurons. We find that the order of firing among neurons during a period of NREM sleep reflects their relative firing rates during prior wake, and changes as a function of prior learning. We show that learning-dependent pattern formation (e.g. “replay”) in the hippocampus during NREM, together with spike timing dependent plasticity (STDP), restructures network activity in a manner similar to that observed in brain circuits across periods of sleep. This suggests that sleep actively promotes memory consolidation by switching the network from rate-based to firing phase-based information encoding.

Cerebellar outputs contribute to spontaneous and movement-related activity in the motor cortex of monkeys

Cerebellar outputs originate from the dentate nucleus (DN), project to the primary motor cortex (M1) via the motor thalamus, control M1 activity, and play an essential role in coordinated movements. However, it is unclear when and how the cerebellar outputs contribute to M1 activity. To address this question, we examined the response of M1 neurons to electrical stimulation of the DN and M1 activity during performance of arm-reaching tasks. Based on response patterns to DN stimulation, M1 neurons were classified into facilitation-, suppression-, and no-response-types. During tasks, not only facilitation- and suppression-type M1 neurons, but also no response-type M1 neurons increased or decreased their firing rates in relation to arm reaching movements. However, the firing rates of facilitation- and suppression-type neurons were higher than those of no-response-type neurons during both inter-trial intervals and arm reaching movements. These results imply that cerebellar outputs contribute to both spontaneous and movement-related activity in the M1, which help to maintain muscle tones and execute coordinated movements, although other inputs also contribute to movement-related activity. Pharmacological inactivation of the DN supports this notion, in that DN inactivation reduced both spontaneous firing rates and movement-related activity in the M1.

The effects of local forearm heating and cooling on motor unit properties during submaximal contractions.

What is the central question of this study? How do temperature manipulations affect motor unit (MU) properties during submaximal contractions to the same relative percentage of maximal force? What is the main finding and its importance? MU recruitment patterns are affected by temperature manipulations at the forearm. However, the relationship between MU potential amplitude and recruitment threshold indicates no change to the order or recruitment. Additionally, the MU potential amplitude and firing rate relationship was affected by temperature, suggesting that smaller MUs are more affected by temperature changes than larger MUs. Temperature impacts muscle contractile properties, such that experiments with workloads based on thermoneutral values will produce different relative intensities if maximal force changes due to muscle temperature. We investigated how temperature affected motor unit (MU) properties with contractions performed at the same normalized percentage of maximal force. Twenty participants (10 females) completed evoked, maximal, and trapezoidal voluntary contractions during thermoneutral-, hot-, and cold-temperature conditions. Forearm temperature was established using 25min of neutral (∼32°C), hot (∼44°C) or cold (∼13°C) water circulated through a tube-lined sleeve. Flexor carpi radialis MU properties were assessed with contractions at 30% and 60% MVC relative to each temperature using surface electromyography decomposition. Changes to contractile properties and electromechanical delay from the evoked twitch suggest that muscle contractility was changed from the thermal manipulations (effect size (d)≥0.42, P<0.05). Maximal force was not different between neutral and hot conditions (d=0.16, P>0.05) but decreased in the cold (d≥0.34, P<0.05). For both contraction intensities, MU potential (MUP) amplitude was larger and duration was longer in the cold compared to neutral and hot conditions (d≥1.24, P<0.05). Cumulative probability density for the number of MUs recruited revealed differences in MU recruitment patterns among temperature conditions. The relationship between MU recruitment threshold and firing rate or MUP amplitude was not different among temperature conditions (P>0.05); however, the relationship between MUP amplitude and firing rate was (P<0.05). Local temperature manipulations appear to affect MU recruitment patterns, which may act as compensatory mechanisms to the changes in muscle viscosity and contractile properties due to local temperature changes.

Synthesis of Hemispheric ITD Tuning from the Readout of a Neural Map: Commonalities of Proposed Coding Schemes in Birds and Mammals.

A major cue to infer sound direction is the difference in arrival time of the sound at the left and right ears, called interaural time difference (ITD). The neural coding of ITD and its similarity across species have been strongly debated. In the barn owl, an auditory specialist relying on sound localization to capture prey, ITDs within the physiological range determined by the head width are topographically represented at each frequency. The topographic representation suggests that sound direction may be inferred from the location of maximal neural activity within the map. Such topographical representation of ITD, however, is not evident in mammals. Instead, the preferred ITD of neurons in the mammalian brainstem often lies outside the physiological range and depends on the neuron's best frequency. Because of these disparities, it has been assumed that how spatial hearing is achieved in birds and mammals is fundamentally different. However, recent studies reveal ITD responses in the owl's forebrain and midbrain premotor area that are consistent with coding schemes proposed in mammals. Particularly, sound location in owls could be decoded from the relative firing rates of two broadly and inversely ITD-tuned channels. This evidence suggests that, at downstream stages, the code for ITD may not be qualitatively different across species. Thus, while experimental evidence continues to support the notion of differences in ITD representation across species and brain regions, the latest results indicate notable commonalities, suggesting that codes driving orienting behavior in mammals and birds may be comparable.

Altered slow (

The 3xTg-AD mouse model reproduces the main features associated with the etiology of familial Alzheimer's disease (AD). To investigate whether these features imply functional cortical network alterations and their evolution with age, we studied spontaneous slow oscillations, activity that integrates cellular and network properties. We quantified different parameters of the emergent slow oscillations—alternating Up and Down states—and of the embedded beta-gamma rhythms of 3xTg-AD and wild-type mice at 7 and 20 months of age. Most group differences occurred at 20 months of age: 3xTg-AD mice presented lower oscillatory frequency, higher cycle variability, and reduced relative (Up/Down) firing rate with respect to controls. The high-frequency analysis revealed a shift toward lower frequencies in older 3xTg-AD animals, reminiscent of one of the electroencephalography hallmarks of patients with AD. This first systematic characterization of the cortical emergent rhythms in 3xTg-AD strain provides insights into the network mechanisms underlying associated network activity alterations.

Immediate-early gene Homer1a intranuclear transcription focus intensity as a measure of relative neural activation.

Immediate-early genes (IEGs) exhibit a rapid, transient transcription response to neuronal activation. Fluorescently labeled mRNA transcripts appear as bright intranuclear transcription foci (INF), which have been used as an all-or-nothing indicator of recent neuronal activity; however, it would be useful to know whether INF fluorescence can be used effectively to assess relative activations within a neural population. We quantified the Homer1a (H1a) response of hippocampal neurons to systematically varied numbers of exposures to the same places by inducing male Long-Evans rats to run laps around a track. Previous studies reveal relatively stable firing rates across laps on a familiar track. A strong linear trend (r2 > 0.9) in INF intensity was observed between 1 and 25 laps, after which INF intensity declined as a consequence of dispersion related to the greater elapsed time. When the integrated fluorescence of the entire nucleus was considered instead, the linear relationship extended to 50 laps. However, there was only an approximate doubling of H1a detected for this 50-fold variation in total spiking. Thus, the intranuclear H1a RNA fluorescent signal does provide a relative measure of how many times a set of neurons was activated over a ~10 min period, but the dynamic range and hence signal-to-noise ratios are poor. This low dynamic range may reflect previously reported reductions in the IEG response during repeated episodes of behavior over longer time scales. It remains to be determined how well the H1a signal reflects relative firing rates within a population of neurons in response to a single, discrete behavioral event.

Examination of muscle morphology and neuromuscular function in normal weight and overfat children aged 7-10 years.

This study examined isometric and isokinetic leg extensor strength, muscle size (mCSA) and tissue composition as measured via echo intensity (mEI), and motor unit (MU) firing rates in normal weight (NW) and OF children aged 7-10years. Fourteen NW (eight girls and six boys, BMI: 15.8±1.4kg/m2 ) and 15 OF (10 girls and five boys, BMI: 20.8±2.3kg/m2 ) children volunteered to perform this study. Percentage body fat (%BF) was measured, and mCSA, mEI, and subcutaneous fat (sFAT) of the vastus lateralis (VL) was assessed. MU mean firing rates (MFRs) in relation to recruitment threshold (RT) of the VL were assessed during submaximal isometric contractions. Maximal isokinetic contractions were performed at 1.05 and 4.20rad/s. The 95% confidence intervals (CI) from the statistical tests are presented. The OF children had greater %BF (95% CI=-15.1 to -7.2), mCSA (95% CI=-4.1 to -1.2), mEI (95% CI=-22.3 to -5.9), and sFAT (95% CI=-0.5 to -0.1), greater rate of strength loss with increasing isokinetic velocities (95% CI=0.4 to 5.4), and a smaller range of MFRs (95% CI=0.007 to 7.136) at the steady torque than the NW children. The OF children had poorer muscle tissue composition, greater velocity-related impairments in muscle strength, and a smaller range of MFRs at the targeted torque that may suggest altered MU recruitment strategies. Interventions in OF children should include exercises and recruit higher-threshold MUs, such as high-intensity resistance exercises.

Investigating the Correlation\u2013Firing Rate Relationship in Heterogeneous Recurrent Networks

The structure of spiking activity in cortical networks has important implications for how the brain ultimately codes sensory signals. However, our understanding of how network and intrinsic cellular mechanisms affect spiking is still incomplete. In particular, whether cell pairs in a neural network show a positive (or no) relationship between pairwise spike count correlation and average firing rate is generally unknown. This relationship is important because it has been observed experimentally in some sensory systems, and it can enhance information in a common population code. Here we extend our prior work in developing mathematical tools to succinctly characterize the correlation and firing rate relationship in heterogeneous coupled networks. We find that very modest changes in how heterogeneous networks occupy parameter space can dramatically alter the correlation–firing rate relationship.

Myosin Heavy Chain Influences Firing Rate Behavior from Moderate to High Intensity Targeted Forces

PURPOSE: It is suggested the ratio of myosin heavy chain (MHC) isoforms and their influence on twitch forces and fatigability effect motor unit (MU) behavior. However, no study has correlated changes in MU firing rates among moderate- to high-intensity contractions with MHC area in vivo. METHODS: Twelve individuals (age=20.89±2.52 yrs, weight=72.03±14.02 kg) performed 3 isometric maximal voluntary contractions (MVC) of the leg extensors on an isokinetic dynamometer followed by randomly ordered isometric muscle actions at 50, 70, and 90% MVC. An electromyographic (EMG) sensor was placed over the VL. EMG signals were decomposed to extract action potentials and firing events of single MUs. Only MUs with > 90% accuracy were used for analysis. Recruitment thresholds (REC Thresh) and mean firing rates (MFR) were calculated for each MU. MFR was calculated as the average value of the MFR trajectory during steady force. Subjects gave a muscle biopsy of the VL. Type I %MHC area was determined by SDS-PAGE. Linear regressions were performed for the 50% MVC, whereas inverse exponential regressions were performed on the 70% and 90% MVC to determine the slopes and y-intercepts for the MFR vs REC Thresh relationships. Predicted firing rates at target force were calculated from the regression equations for each subject for MUs with a REC threshold of 5-45% MVC in 5% increments. To examine changes in MU firing rates in relation to REC Thresh, predicted firing rates from the 70% and 90% MVC were normalized to the predicted firing rate value for the 50% MVC. For each REC Thresh, linear regressions were performed on the normalized firing rate values vs contraction intensity. Pearson’s product moment correlations were calculated comparing the slopes and type I %MHC area. Alpha was set at 0.05. RESULTS: Pearson’s product moment correlations were significant among type I %MHC area and the slopes of the change in predicted firing rates vs contraction intensity for MUs with a REC thresh of 35, 40, and 45% MVC (P < 0.05; R = -0.754 to -0.669). CONCLUSIONS: Individuals with lower percentages of type I MHC area had greater increases in MU firing rates with increments in targeted forces for MUs with REC Thresh of 35 - 45% MVC. This may indicate that MU firing rate and recruitment patterns differ as a function of MHC area.

A Novel Mechanism for the Grid-to-Place Cell Transformation Revealed by Transgenic Depolarization of Medial Entorhinal Cortex Layer II

The spatial receptive fields of neurons in medial entorhinal cortex layer II (MECII) and in the hippocampus suggest general and environment-specific maps ofspace, respectively. However, the relationship between these receptive fields remains unclear. We reversibly manipulated the activity of MECII neurons via chemogenetic receptors and compared the changes in downstream hippocampal place cells tothose of neurons in MEC. Depolarization of MECIIimpaired spatial memory and elicited drastic changes in CA1 place cells in a familiar environment, similar to those seen during remapping between distinct environments, while hyperpolarization did not. In contrast, both manipulations altered the firing rate of MEC neurons without changing their firing locations. Interestingly, only depolarization caused significant changes in the relative firing rates of individual grid fields, reconfiguring the spatial input from MEC. This suggests a novel mechanism of hippocampal remapping whereby rate changes in MEC neurons lead to locational changes of hippocampal place fields.

Acute Effects of Vibration on Recruitment Threshold versus Peak Firing Rate Relationship during Isometric Contraction

PURPOSE:This study examined the acute effects of vibration (VIB) on motor unit (MU) behavior of the vastus lateralis (VL) during 40% maximal voluntary contraction (MVC). METHODS:Five males (age= 22.0±2.4 yrs) and three women (age=20.7±3.1 yrs) volunteered for this study. An electromyographic (EMG) sensor was placed over the VL. Participants preformed 3 isometric MVCs followed by isometric trapezoid muscle actions at 40% MVC (CON). Procedures were preformed twice separated by 3-5 days. VIB was then applied at 55 Hz. to the patella tendon for 10 min. prior to testing and continued throughout the remainder of testing, including a 40% MVC (VIB) at the same absolute force as the 40% CON. Decomposition techniques were applied to the EMG signals to extract action potentials and firing events of single MU. Only MUs decomposed with accuracies >92% were included for analysis. Linear regressions were performed on the MU recruitment threshold (REC) vs. peak firing rate (PFR) relationships during the first, middle, and final sec of the steady force segment for each subject. Slopes and y-intercepts were calculated for each subject and time point. Two separate 2-way repeated measures ANOVAs (treatment [CON vs. VIB] x time [first vs. middle vs. final sec]) were used to examine possible differences among y-intercepts and slopes. When appropriate, follow-up analyses for the ANOVA models were preformed using paired samples t-test with Bonferroni corrections. The level of significance was set at P ≤ 0.05. RESULTS:The analyses for the y-intercepts indicated that there was no 2-way interaction (P = 0.681) and no main effect for time (P = 0.803), however, there was a main effect for treatment (P = 0.047). The y-intercepts were greater for the VIB (29.49 ± 1.74 pps) than CON (26.49 ± 1.83 pps). The analyses for the slopes indicated no 2-way interaction (P = 0.684) or main effects for time (P = 0.729) and treatment (P = 0.055). CONCLUSIONS:The firing rates of the motoneuron pool were greater during VIB than the CON at the same absolute force. Thus, supporting the hypothesis that muscle spindles provide inhibitory effects on MU firing rates. When Ia afferent feedback from muscle spindles is removed the firing rates of the motoneuron pool increase. In addition, there was no time-dependent alterations in the REC vs. PFR relationships as function of VIB.

Dynamical state of the network determines the efficacy of single neuron properties in shaping the network activity.

Spike patterns are among the most common electrophysiological descriptors of neuron types. Surprisingly, it is not clear how the diversity in firing patterns of the neurons in a network affects its activity dynamics. Here, we introduce the state-dependent stochastic bursting neuron model allowing for a change in its firing patterns independent of changes in its input-output firing rate relationship. Using this model, we show that the effect of single neuron spiking on the network dynamics is contingent on the network activity state. While spike bursting can both generate and disrupt oscillations, these patterns are ineffective in large regions of the network state space in changing the network activity qualitatively. Finally, we show that when single-neuron properties are made dependent on the population activity, a hysteresis like dynamics emerges. This novel phenomenon has important implications for determining the network response to time-varying inputs and for the network sensitivity at different operating points.

Reliability of Motor Unit Recruitment Threshold versus Mean Firing Rate Relationship during a Submaximal Contraction

PURPOSE: This study examined the reliability of motor unit (MU) recruitment (REC) versus mean firing rates (MFR) relationships of the vastus lateralis (VL) during 40% and 70% maximal voluntary contractions (MVC). METHODS: Eight healthy men (age=21.63±2.39 yrs) and six healthy women (age=19.67±1.37 yrs) volunteered for this study. An electromyography (EMG) sensor was placed over the VL. Participants performed 3 isometric MVC followed by isometric trapezoid muscle actions at 40% and 70% MVC. These procedures were performed twice separated by 3-5 days. Decomposition techniques were applied to the EMG signals to extract action potentials and firing events of single MUs. The REC thresholds and MFRs were calculated for each MU. Only MUs decomposed with accuracies >95% were included for analysis. Linear regressions were performed on the REC versus MFR relationships. Reliability statistics were calculated for the slopes and y-intercepts from the REC versus MFR relationships across days 1 and 2. Intraclass correlation coefficients (ICC) model “2,1”, standard error of the measurements (SEM), and repeated measures ANOVAs were calculated to assess reliability. RESULTS: There were no significant differences between the slopes and y-intercepts for the 70% MVC (P>0.05). The ICCs and SEM (expressed as a percentage of the mean, %) from the 70% MVC were 0.91 and 25.00% and 0.79 and 15.58% for the slope and y-intercept, respectively. Reliability statistics could not be calculated for the 40% MVC as there was a small number of subjects (1) that had sufficient MUs (>5 MUs) for each day. CONCLUSIONS: The ICCs and SEMs indicated good reliability from the 70% MVC when including MUs with accuracies >95%, however, with strict accuracy criteria there were no reliability statistics calculated for the 40% MVC. The VL is a mixed fiber type muscle that recruits MUs up to 90-95% MVC. Although speculative, during low force contractions the majority of active MUs (low threshold MUs) may be deeper in the muscle and more difficult to accurately quantify. In addition, the high threshold MUs are located in the superficial intramuscular region and are progressively activated at higher contraction intensities and, thus are not contributing to the surface EMG signal at lower contraction intensities.

The neural code for auditory space depends on sound frequency and head size in an optimal manner.

A major cue to the location of a sound source is the interaural time difference (ITD)–the difference in sound arrival time at the two ears. The neural representation of this auditory cue is unresolved. The classic model of ITD coding, dominant for a half-century, posits that the distribution of best ITDs (the ITD evoking a neuron’s maximal response) is unimodal and largely within the range of ITDs permitted by head-size. This is often interpreted as a place code for source location. An alternative model, based on neurophysiology in small mammals, posits a bimodal distribution of best ITDs with exquisite sensitivity to ITDs generated by means of relative firing rates between the distributions. Recently, an optimal-coding model was proposed, unifying the disparate features of these two models under the framework of efficient coding by neural populations. The optimal-coding model predicts that distributions of best ITDs depend on head size and sound frequency: for high frequencies and large heads it resembles the classic model, for low frequencies and small head sizes it resembles the bimodal model. The optimal-coding model makes key, yet unobserved, predictions: for many species, including humans, both forms of neural representation are employed, depending on sound frequency. Furthermore, novel representations are predicted for intermediate frequencies. Here, we examine these predictions in neurophysiological data from five mammalian species: macaque, guinea pig, cat, gerbil and kangaroo rat. We present the first evidence supporting these untested predictions, and demonstrate that different representations appear to be employed at different sound frequencies in the same species.

Alteration of neural action potential patterns by axonal stimulation: the importance of stimulus location

Objective. Stimulation of peripheral nerves is often superimposed on ongoing motor and sensory activity in the same axons, without a quantitative model of the net action potential train at the axon endpoint. Approach. We develop a model of action potential patterns elicited by superimposing constant frequency axonal stimulation on the action potentials arriving from a physiologically activated neural source. The model includes interactions due to collision block, resetting of the neural impulse generator, and the refractory period of the axon at the point of stimulation. Main results. Both the mean endpoint firing rate and the probability distribution of the action potential firing periods depend strongly on the relative firing rates of the two sources and the intersite conduction time between them. When the stimulus rate exceeds the neural rate, neural action potentials do not reach the endpoint and the rate of endpoint action potentials is the same as the stimulus rate, regardless of the intersite conduction time. However, when the stimulus rate is less than the neural rate, and the intersite conduction time is short, the two rates partially sum. Increases in stimulus rate produce non-monotonic increases in endpoint rate and continuously increasing block of neurally generated action potentials. Rate summation is reduced and more neural action potentials are blocked as the intersite conduction time increases. At long intersite conduction times, the endpoint rate simplifies to being the maximum of either the neural or the stimulus rate. Significance. This study highlights the potential of increasing the endpoint action potential rate and preserving neural information transmission by low rate stimulation with short intersite conduction times. Intersite conduction times can be decreased with proximal stimulation sites for muscles and distal stimulation sites for sensory endings. The model provides a basis for optimizing experiments and designing neuroprosthetic interventions involving motor or sensory stimulation.

The contribution of synaptic location to inhibitory gain control in pyramidal cells

The activity of pyramidal cells is controlled by two opposing forces: synaptic inhibition and synaptic excitation. Interestingly, these synaptic inputs are not distributed evenly across the dendritic trees of cortical pyramidal cells. Excitatory synapses are densely packed along only the more peripheral dendrites, but are absent from the proximal stems and the soma. In contrast, inhibitory synapses are located throughout the dendritic tree, the soma, and the axon initial segment. Thus both excitatory and inhibitory inputs exist on the peripheral dendritic tree, while the proximal segments only receive inhibition. The functional consequences of this uneven organization remain unclear. We used both optogenetics and dynamic patch clamp techniques to simulate excitatory synaptic conductances in pyramidal cells, and then assessed how their firing output is modulated by gamma-amino-butyric acid type A (GABAA) receptor activation at different regions of the somatodendritic axis. We report here that activation of GABAA receptor on the same dendritic compartment as excitatory inputs causes a rightwards shift in the function relating firing rate to excitatory conductance (the input–output function). In contrast, GABAA receptor activation proximal to the soma causes both a rightwards shift and also a reduction in the maximal firing rate. The experimental data are well reproduced in a simple, four compartmental model of a neuron with inhibition either on the same compartment, or proximal, to the excitatory drive.

Iontophoretic application of an A-type potassium channel blocker to the trigeminal ganglion neurons enhances the excitability of Aδ- and C-neurons innervating the temporomandibular joint in rats

The present study tested the hypothesis that under in vivo conditions the iontophoretic application of a IA channel blocker, 4-aminopyridine (4-AP), to the TRG neurons changes the properties of Aδ-/C-TRG neurons that innervate the temporomandibular joint (TMJ) region, using extracellular electrophysiological recording with multi-barrel electrodes in pentobarbital-anesthetized rats. A total of twenty-one neurons (Aδ-: 76%; C-: 24%) responded to electrical stimulation of the TMJ region in pentobarbital-anesthetized rats. TMJ electrical stimulation-induced discharges of Aδ/C-neurons were significantly potentiated in current dependent manner (30–70nA) by iontophoretic application of 4-AP into the TRGs. The spontaneous firing rates of Aδ- and C-neurons were also increased by 4-AP in a current-dependent manner (30–70nA). The mean threshold current that evoked spontaneous discharges of C-neurons was significantly lower than that of Aδ-neurons. Moreover, the mean relative threshold current for electrical stimulation of TMJ-induced response of C-TRG neurons was significantly lower than that of Aδ-neuron. The relative firing rate of C-neurons induced by 4-AP-treatment (70nA) was significantly higher than for Aδ-neurons. These results suggest that the application of 4-AP enhanced Aδ/C-TRG neuronal activities innervating the TMJ in vivo and C-neurons had significantly higher sensitivity for 4-AP than Aδ-neurons.