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The olfactory tubercle (OT) is a unique part of the olfactory cortex of the mammal brain in that it is also a component of the ventral striatum. It is crucially involved in motivational behaviors, particularly in adaptive olfactory learning. This review introduces the basic properties of the OT, its synaptic connectivity with other brain areas, and the plasticity of the connectivity associated with learning behavior. The adaptive properties of olfactory behavior are discussed further based on the characteristics of OT neuronal circuits. [ABSTRACT FROM AUTHOR]

The purpose of the study was to investigate the influence of contraction history on force steadiness and the associated EMG activity during submaximal isometric contractions performed with the dorsiflexor muscles. The key feature of the protocol was a triangular ramp contraction performed in the middle of a steady contraction at a lower target force. The target force during the ramp contraction was 20% MVC greater than that during the steady contraction. Thirty-seven healthy individuals (21 men and 16 women) performed the submaximal tasks with the ankle dorsiflexors. Electromyography (EMG) signals were recorded from tibialis anterior with a pair of surface electrodes. The coefficient of variation for force was significantly greater during the second steady contraction compared with the first one at each of the seven target forces (p < 0.015; d = 0.38–0.92). Although the average applied force during the steady contractions before and after the triangular contraction was the same (p = 0.563), the mean EMG amplitude for the steady contractions performed after the triangular contraction was significantly greater at each of the seven target forces (p < 0.0001; d = 0.44–0.68). Also, there were significant differences in mean EMG frequency between the steady contractions performed before and after the triangular contraction (p < 0.01; d = 0.13–0.82), except at 10 and 20% MVC force. The greater force fluctuations during a steady submaximal contraction after an intervening triangular contraction indicate a change in the discharge characteristics of the involved motor units. [ABSTRACT FROM AUTHOR]

Male and female rats differ in muscle fibre composition, related motor unit contractile properties, and muscle spindle density but not number. On the other hand, their motoneurons' intrinsic properties, excitability and firing properties are similar. The aim of this study was to investigate whether apparent sex differences in body mass and muscle force influence the proprioceptive input from muscle spindles to motoneurons. Medial gastrocnemius motoneurons were investigated intracellularly in deeply anaesthetised male and female rats. Monosynaptic Ia excitatory postsynaptic potentials (EPSPs) were evoked using electrical stimulation of primary afferents from homonymous muscle. Data were analysed using a mixed linear model. The central latencies of EPSPs were 0.38–0.80 ms, with no differences in means between males and females. The maximum EPSP amplitude varied between 2.03 and 8.09 mV in males and 1.24 and 6.79 mV in females. The mean maximum EPSP amplitude was 26% higher in males than in females. The mean EPSP rise time, half‐decay time and total duration did not differ between the sexes. EPSP amplitudes correlated with the resting membrane potential, input resistance and EPSP rise time in both sexes. The observed sex differences in the Ia proprioceptive input may be related either to mechanical loading differences in males and females associated with their different body mass or hormonal differences influencing the levels of neuromodulation in spinal circuits. The results highlight the importance of taking sex into consideration in the studies on the influence of afferent inputs on MN excitability. [ABSTRACT FROM AUTHOR]

Oxytocin (Oxt) neurons regulate diverse physiological responses via direct connections with different neural circuits. However, the lack of comprehensive input-output wiring diagrams of Oxt neurons and their quantitative relationship with Oxt receptor (Oxtr) expression presents challenges to understanding circuit-specific Oxt functions. Here, we establish a whole-brain distribution and anatomic connectivity map of Oxt neurons, and their relationship with Oxtr expression using high-resolution 3D mapping methods in adult male and female mice. We use a flatmap to describe Oxt neuronal expression in four hypothalamic domains including under-characterized Oxt neurons in the tuberal nucleus (TU). Oxt neurons in the paraventricular hypothalamus (PVH) broadly project to nine functional circuits that control cognition, brain state, and somatic visceral response. In contrast, Oxt neurons in the supraoptic (SO) and accessory (AN) nuclei have limited central projection to a small subset of the nine circuits. Surprisingly, quantitative comparison between Oxt output and Oxtr expression showed no significant correlation across the whole brain, suggesting abundant indirect Oxt signaling in Oxtr-expressing areas. Unlike output, Oxt neurons in both the PVH and SO receive similar monosynaptic inputs from a subset of the nine circuits mainly in the thalamic, hypothalamic, and cerebral nuclei areas. Our results suggest that PVH-Oxt neurons serve as a central modulator to integrate external and internal information via largely reciprocal connection with the nine circuits while the SO-Oxt neurons act mainly as unidirectional Oxt hormonal output. In summary, our Oxt wiring diagram provides anatomic insights about distinct behavioral functions of Oxt signaling in the brain. [ABSTRACT FROM AUTHOR]

• Inhibitory conductances are underestimated more than excitatory conductances. • Estimation of synaptic conductances is worse during high levels of background input. • The time course of estimated excitatory and inhibitory conductances is distorted. • Space clamp errors are exacerbated by dendritic voltage-activated conductances. The whole-cell voltage clamp technique is commonly used to estimate synaptic conductances. While previous work has shown how these estimates are affected by series resistance and space clamp errors during isolated synaptic events, how voltage clamp errors impact on synaptic conductance estimates during concurrent excitation and inhibition is less clear. This issue is particularly relevant given that many studies now use the whole-cell voltage clamp technique to estimate synaptic conductances in vivo , where both excitation and inhibition are intact. Using both simplistic and morphologically realistic models, we investigate how imperfect voltage clamp conditions distort estimates of excitatory and inhibitory synaptic conductance estimated using the Borg-Graham method during concurrent synaptic input onto dendrites. These simulations demonstrate that dendritically located conductances are underestimated even when dynamic clamp reinjection faithfully reproduces the voltage response at the soma to the actual conductances. Inhibitory conductances are underestimated more than excitatory conductances, leading to errors in the excitatory to inhibitory conductance ratio and negative inhibitory conductance estimates during distal inhibition. Interactions between unclamped dendritic excitatory and inhibitory conductances also introduce correlations when the actual conductances are uncorrelated, as well as distortions in the time course of estimated excitatory and inhibitory conductances. Finally, we show that space clamp errors are exacerbated by the inclusion of dendritic voltage-activated conductances. In summary, we highlight issues with the interpretation of synaptic conductance estimates obtained using somatic whole-cell voltage clamp during concurrent excitatory and inhibitory input to neurons with dendrites. [ABSTRACT FROM AUTHOR]

Key points: Recently, we found that the dorsal vagal complex displays autonomous circadian timekeeping properties The dorsal motor nucleus of the vagus (DMV) is an executory part of this complex – a source of parasympathetic innervation of the gastrointestinal tract Here, we reveal daily changes in the neuronal activities of the rat DMV, including firing rate, intrinsic excitability and synaptic input – all of these peaking in the late day Additionally, we establish that short term high‐fat diet disrupts these daily rhythms, boosting the variability in the firing rate, but blunting the DMV responsiveness to ingestive cues These results help us better understand daily control over parasympathetic outflow and provide evidence on its dependence on the high‐fat diet The suprachiasmatic nuclei (SCN) of the hypothalamus function as the brain's primary circadian clock, but circadian clock genes are also rhythmically expressed in several extra‐SCN brain sites where they can exert local temporal control over physiology and behaviour. Recently, we found that the hindbrain dorsal vagal complex possesses strong daily timekeeping capabilities, with the area postrema and nucleus of the solitary tract exhibiting the most robust clock properties. The possibility that the executory part of this complex – the dorsal motor nucleus of the vagus (DMV) – also exhibits daily changes has not been extensively studied. The DMV is the source of vagal efferent motoneurons that regulate gastric motility and emptying and consequently influence meal size and energy homeostasis. We used a combination of multi‐channel electrophysiology and patch clamp recordings to gain insight into effects of time of day and diet on these DMV cells. We found that DMV neurons increase their spontaneous activity, excitability and responsiveness to metabolic neuromodulators at late day and this was paralleled with an enhanced synaptic input to these neurons. A high‐fat diet typically damps circadian rhythms, but we found that consumption of a high‐fat diet paradoxically amplified daily variation of DMV neuronal activity, while blunting the neurons responsiveness to metabolic neuromodulators. In summary, we show for the first time that DMV neural activity changes with time of day, with this temporal variation modulated by diet. These findings have clear implications for our understanding of the daily control of vagal efferents and parasympathetic outflow. [ABSTRACT FROM AUTHOR]

During activity-dependent potentiation (ADP), motor unit firing rates (MUFRs) are lower; however, the mechanism for this response is not known. During increasing torque isometric contractions at low contraction intensities, MUFR trajectories initially accelerate and saturate demonstrating a nonlinear response due to the activation of persistent inward currents (PICs) at the motoneuron. The purpose was to assess whether PICs are a factor in the reduction of MUFRs during ADP. To assess this, MUFR trajectories were fit with competing functions of linear regression and a rising exponential (i.e., acceleration and saturation). With fine-wire electrodes, discrete MU potential trains were recorded in the tibialis anterior during slowly increasing dorsiflexion contractions to 10% of maximal voluntary contraction following both voluntary [postactivation potentiation (PAP)] and evoked [posttetanic potentiation (PTP)] contractions. In eight participants, 25 MUs were recorded across both ADP conditions and compared with the control with no ADP effect. During PAP and PTP, the average MUFRs were 16.4% and 9.2% lower (both P ≤ 0.001), respectively. More MUFR trajectories were better fit to the rising exponential during control (16/25) compared with PAP (4/25, P < 0.001) and PTP (8/25, P = 0.03). The MU samples that had a rising exponential MUFR trajectory during PAP and PTP displayed an ~11% lower initial acceleration compared with control (P < 0.05). Thus, presumed synaptic amplification and MUFR saturation due to PIC properties are attenuated during ADP regardless of the type of conditioning contraction. This response may contribute to lower MUFRs and likely occurred because synaptic input is reduced when contractile function is enhanced. [ABSTRACT FROM AUTHOR]

Whole body vibration (WBV) is often applied as an alternative method for strength training or to prevent muscle force decrease. In this study, we evaluated the influence of WBV on Ia monosynaptic input from muscle spindles because the tonic vibration reflex is responsible for the enhancement of muscle activity observed after WBV. The aim was to investigate whether repeated activation of muscle spindles during WBV may result in altered synaptic excitation of motoneurons. WBV was performed on adult male Wistar rats, 5 days/wk, for 5 wk, and each daily session consisted of four 30-s runs of vibration at 50 Hz. Fast-type medial gastrocnemius motoneurons were investigated intracellularly in deeply anesthetized animals in the experimental (n = 7, 34 motoneurons) and control (n = 7, 32 motoneurons) groups. Monosynaptic Ia excitatory postsynaptic potentials (EPSPs) were evoked by electrical stimulation of afferent fibers from the synergistic lateral gastrocnemius and soleus muscles. Data were analyzed using a mixed linear model. The central latencies of EPSPs were 0.45–0.9 ms with no differences in the mean values between the analyzed groups (P = 0.291). WBV induced an increase of the mean EPSP amplitude by 28% (P = 0.025), correlated with the resting membrane potential and input resistance, and a shortening of the mean EPSP rise time by 11% (P = 0.012). The potentiation of synaptic excitation of motoneurons was not accompanied by changes of passive membrane properties, pointing to synaptic plasticity. This indicates that WBV may support rehabilitation or training processes aimed at increasing muscle strength on the basis of increased motoneuronal drive. [ABSTRACT FROM AUTHOR]

Neurons in the developing visual cortex undergo progressive functional maturation as indicated by the refinement of their visual feature selectivity. However, changes of the synaptic architecture underlying the maturation of spatial visual receptive fields (RFs) per se remain largely unclear. Here, loose-patch as well as single-unit recordings in layer 4 of mouse primary visual cortex (V1) of both sexes revealed that RF development following an eye-opening period is marked by an increased proportion of cortical neurons with spatially defined RFs, together with the increased signal-to-noise ratio of spiking responses. By exploring excitatory and inhibitory synaptic RFs with whole-cell voltage-clamp recordings, we observed a balanced enhancement of both synaptic excitation and inhibition, and while the excitatory subfield size remains relatively constant during development, the inhibitory subfield is broadened. This balanced developmental strengthening of excitatory and inhibitory synaptic inputs results in enhanced visual responses, and with a reduction of spontaneous firing rate, contributes to the maturation of visual cortical RFs. Visual deprivation by dark rearing impedes the normal strengthening of excitatory inputs but leaves the apparently normal enhancement of inhibition while preventing the broadening of the inhibitory subfield, leading to weakened RF responses and a reduced fraction of neurons exhibiting a clear RF, compared with normally reared animals. Our data demonstrate that an experience-dependent and coordinated maturation of excitatory and inhibitory circuits underlie the functional development of visual cortical RFs. [ABSTRACT FROM AUTHOR]

The brain has a never-ending internal activity, whose spatiotemporal evolution interacts with external inputs to constrain their impact on brain activity and thereby how we perceive them. We used reproducible touch-related spatiotemporal sensory inputs and recorded intracellularly from rat (Sprague-Dawley, male) neocortical neurons to characterize this interaction. The synaptic responses, or the summed input of the networks connected to the neuron, varied greatly to repeated presentations of the same tactile input pattern delivered to the tip of digit 2. Surprisingly, however, these responses tended to sort into a set of specific time-evolving response types, unique for each neuron. Further, using a set of eight such tactile input patterns, we found each neuron to exhibit a set of specific response types for each input provided. Response types were not determined by the global cortical state, but instead likely depended on the time-varying state of the specific subnetworks connected to each neuron. The fact that some types of responses recurred indicates that the cortical network had a non-continuous landscape of solutions for these tactile inputs. Therefore, our data suggest that sensory inputs combine with the internal dynamics of the brain networks, thereby causing them to fall into one of the multiple possible perceptual attractor states. The neuron-specific instantiations of response types we observed suggest that the subnetworks connected to each neuron represent different components of those attractor states. Our results indicate that the impact of cortical internal states on external inputs is substantially more richly resolvable than previously shown.

The brain has a never-ending internal activity, whose spatiotemporal evolution interacts with external inputs to constrain their impact on brain activity and thereby how we perceive them. We used reproducible touch-related spatiotemporal sensory inputs and recorded intracellularly from rat (Sprague-Dawley, male) neocortical neurons to characterize this interaction. The synaptic responses, or the summed input of the networks connected to the neuron, varied greatly to repeated presentations of the same tactile input pattern delivered to the tip of digit 2. Surprisingly, however, these responses tended to sort into a set of specific time-evolving response types, unique for each neuron. Further, using a set of eight such tactile input patterns, we found each neuron to exhibit a set of specific response types for each input provided. Response types were not determined by the global cortical state, but instead likely depended on the time-varying state of the specific subnetworks connected to each neuron. The fact that some types of responses recurred indicates that the cortical network had a non-continuous landscape of solutions for these tactile inputs. Therefore, our data suggest that sensory inputs combine with the internal dynamics of the brain networks, thereby causing them to fall into one of the multiple possible perceptual attractor states. The neuron-specific instantiations of response types we observed suggest that the subnetworks connected to each neuron represent different components of those attractor states. Our results indicate that the impact of cortical internal states on external inputs is substantially more richly resolvable than previously shown. [ABSTRACT FROM AUTHOR]

The initial increases in force production with resistance training are thought to be primarily underpinned by neural adaptations. This notion is firmly supported by evidence displaying motor unit adaptations following resistance training; however, the precise locus of neural adaptation remains elusive. The purpose of this review is to clarify and critically discuss the literature concerning the site(s) of putative neural adaptations to short-term resistance training. The proliferation of studies employing non-invasive stimulation techniques to investigate evoked responses have yielded variable results, but generally support the notion that resistance training alters intracortical inhibition. Nevertheless, methodological inconsistencies and the limitations of techniques, e.g. limited relation to behavioural outcomes and the inability to measure volitional muscle activity, preclude firm conclusions. Much of the literature has focused on the corticospinal tract; however, preliminary research in non-human primates suggests reticulospinal tract is a potential substrate for neural adaptations to resistance training, though human data is lacking due to methodological constraints. Recent advances in technology have provided substantial evidence of adaptations within a large motor unit population following resistance training. However, their activity represents the transformation of afferent and efferent inputs, making it challenging to establish the source of adaptation. Whilst much has been learned about the nature of neural adaptations to resistance training, the puzzle remains to be solved. Additional analyses of motoneuron firing during different training regimes or coupling with other methodologies (e.g., electroencephalography) may facilitate the estimation of the site(s) of neural adaptations to resistance training in the future. [ABSTRACT FROM AUTHOR]

Serotonergic neurons play key roles in various biological processes. However, circuit mechanisms underlying tight control of serotonergic neurons remain largely unknown. Here, we systematically investigated the organization of long-range synaptic inputs to serotonergic neurons and GABAergic neurons in the dorsal raphe nucleus (DRN) of mice with a combination of viral tracing, slice electrophysiological, and optogenetic techniques. We found that DRN serotonergic neurons and GABAergic neurons receive largely comparable synaptic inputs from six major upstream brain areas. Upon further analysis of the fine functional circuit structures, we found both bilateral and ipsilateral patterns of topographic connectivity in the DRN for the axons from different inputs. Moreover, the upstream brain areas were found to bidirectionally control the activity of DRN serotonergic neurons by recruiting feedforward inhibition or via a push-pull mechanism. Our study provides a framework for further deciphering the functional roles of long-range circuits controlling the activity of serotonergic neurons in the DRN.

• Pontine neurons in a medial parabrachial (PB) subregion control breathing frequency. • ∼54% of medullary VRC neurons receive synaptic input from the PB subregion. • preBötC I- and pre-I neurons are mainly excited by brief PB subregion synaptic inputs. • BötC Expiratory neurons are strongly inhibited by brief PB subregion synaptic inputs. • E-to-I phase transition is advanced by combined I-excitation and E-inhibition. Neurons in a subregion of the medial parabrachial (PB) complex control expiratory duration (TE) and the inspiratory on -switch. To better understanding the underlying mechanisms, this study aimed to determine the types of medullary neurons in the rhythmogenic preBötzinger/Bötzinger Complex (preBötC/BötC) and adjacent areas that receive synaptic inputs from the PB subregion and whether these inputs are excitatory or inhibitory in nature. Highly localized electrical stimuli in the PB subregion combined with multi-electrode recordings from respiratory neurons and phrenic nerve activities were used to generate stimulus-to-spike event histograms to detect correlations in decerebrate, vagotomized dogs during isocapnic hyperoxia. Short-time scale correlations were found in 237/442 or ∼54% of the ventral respiratory column (VRC) neurons. Inhibition of E-neurons was ∼2.5X greater than for I-neurons, while Pre-I and I-neurons were excited. These findings indicate that the control of TE and the inspiratory on-switch by the PB subregion are mediated by a marked inhibition of BötC E-neurons combined with an excitation of I-neurons, especially pre-I neurons. [ABSTRACT FROM AUTHOR]

Coherence between electromyographic (EMG) signals is often used to infer the common synaptic input to populations of motor neurons. This analysis, however, may be limited due to the filtering effect of the motor unit action potential waveforms. This study investigated the ability of surface EMG–EMG coherence to predict common synaptic input to motor neurons. Surface and intramuscular EMG were recorded from two locations of the tibialis anterior muscle during steady ankle dorsiflexions at 5 and 10% of the maximal force in 10 healthy individuals. The intramuscular EMG signals were decomposed to identify single motor unit spike trains. For each trial, the strength of the common input in different frequency bands was estimated from the coherence between two cumulative spike trains, generated from sets of single motor unit spike trains (reference measure). These coherence values were compared with those obtained from the coherence between the surface EMG signals (raw, rectified, and high-passed filtered at 250 Hz before rectification) using linear regression. Overall, the high-pass filtering of the EMG prior to rectification did not substantially change the results with respect to rectification only. For both signals, the correlation of EMG coherence with motor unit coherence was strong at 5% MVC (r2 > 0.8; p < 0.01), but only for frequencies > 5 Hz. At 10% MVC, the correlation between EMG and motor unit coherence was only significant for frequencies > 15 Hz (r2 > 0.8; p < 0.01). However, when using raw EMG for coherence analysis, the only significant relation with motor unit coherence was observed for the bandwidth 5–15 Hz (r2 > 0.68; p = 0.04). In all cases, there was no association between motor unit and EMG coherence for frequencies < 5 Hz (r2 ≤ 0.2; p ≥ 0.51). In addition, a substantial error in the best linear fit between motor unit and EMG coherence was always present. In conclusion, high-frequency (>5 Hz) common synaptic inputs to motor neurons can partly be estimated from the rectified surface EMG at low-level steady contractions. The results, however, suggest that this association is weakened with increasing contraction intensity and that input at lower frequencies during steady isometric contractions cannot be detected accurately by surface EMG coherence.

The spatial organization of synaptic inputs on the dendritic tree of cortical neurons is considered to play an important role in the dendritic integration of synaptic activity. Active electrical properties of dendrites and mechanisms of dendritic integration have been studied for a long time. New technological developments are now enabling the characterization of the spatial organization of synaptic inputs on dendrites. However, quantitative methods for the analysis of such data are lacking. In order to place cluster parameters into the framework of dendritic integration and synaptic summation, these parameters need to be assessed rigorously in a quantitative manner. Here I present an approach for the analysis of synaptic input clusters on the dendritic tree that is based on combinatorial analysis of the likelihoods to observe specific input arrangements. This approach is superior to the commonly applied analysis of nearest neighbor distances between synaptic inputs comparing their distribution to simulations with random reshuffling or bootstrapping. First, the new approach yields exact likelihood values rather than approximate numbers obtained from simulations. Second and more importantly, the new approach identifies individual clusters and thereby allows to quantify and characterize individual cluster properties.

Melanopsin‐expressing retinal ganglion cells are intrinsically photosensitive cells that are involved in non‐image forming visual processes such as the pupillary light reflex and circadian entrainment but also contribute to visual perception. Here we used immunohistochemistry to study the morphology, density, distribution, and synaptic connectivity of melanopsin‐expressing ganglion cells in four post mortem human donor retinas. Two types of melanopsin‐expressing ganglion cells were distinguished based on their dendritic stratification near either the outer or the inner border of the inner plexiform layer. Outer stratifying cells make up on average 60% of the melanopsin‐expressing cells. About half of the melanopsin‐expressing cells (or 80% of the outer stratifying cells) have their soma displaced to the inner nuclear layer. Inner stratifying cells have their soma exclusively in the ganglion cell layer and include a small proportion of bistratified cells. The dendritic field diameter of melanopsin‐expressing cells ranges from 250 (near the fovea) to 1,000 µm in peripheral retina. The dendritic trees of outer stratifying cells cover the retina independent of soma location. The dendritic fields of both outer and inner stratifying cells show a high degree of overlap with a coverage factor of approximately two. Melanopsin‐expressing cells occur at an average peak density of between ∼20 and ∼40 cells/mm2 at about 2 mm eccentricity, the density drops to below ∼10 cells/mm2 at about 8 mm eccentricity. Both the outer and inner stratifying dendrites express postsynaptic density (PSD95) immunoreactive puncta suggesting that they receive synaptic input from bipolar cells. Using immunohistochemistry and confocal microscopy the authors describe two morphological types of melanopsin‐expressing cells with overlapping dendritic fields across human retina. Scale bar = 100 ?m. [ABSTRACT FROM AUTHOR]

Key points: Ectopic action potentials (EAPs) arise at distal locations in axonal fibres and are often associated with neuronal pathologies such as epilepsy or nerve injury, but they also occur during physiological network conditions. This study investigates whether initiation of such EAPs is modulated by subthreshold synaptic activity.Somatic subthreshold potentials invade the axonal compartment to considerable distances (>350 μm), whereas spread of axonal subthreshold potentials to the soma is inefficient.Ectopic spike generation is entrained by conventional synaptic signalling mechanisms. Excitatory synaptic potentials promote EAPs, whereas inhibitory synaptic potentials block EAPs.The modulation of ectopic excitability depends on propagation of somatic voltage deflections to the axonal EAP initiation site.Synaptic modulation of EAP initiation challenges the view of the distal axon being independent of synaptic activity and may contribute to mechanisms underlying fast network oscillations and pathological network activity. While most action potentials are generated at the axon initial segment, they can also be triggered at more distal sites along the axon. Such ectopic action potentials (EAPs) occur during several neuronal pathologies such as epilepsy, nerve injuries and inflammation but have also been observed during physiological network activity. EAPs propagate antidromically towards the somato‐dendritic compartment where they modulate synaptic plasticity. Here we investigate the converse signal direction: do somato‐dendritic synaptic potentials affect the generation of ectopic spikes? We measured anti‐ and orthodromic spikes in the soma and axon of mouse hippocampal CA1 pyramidal cells. We found that synaptic potentials propagate reliably through the axon, causing significant voltage transients at distances >350 μm. At these sites, excitatory input efficiently facilitated EAP initiation in distal axons and, conversely, inhibitory input suppressed EAP initiation. Our data reveal a new mechanism by which ectopically generated spikes can be entrained by conventional synaptic signalling during normal and pathological network activity. Key points: Ectopic action potentials (EAPs) arise at distal locations in axonal fibres and are often associated with neuronal pathologies such as epilepsy or nerve injury, but they also occur during physiological network conditions. This study investigates whether initiation of such EAPs is modulated by subthreshold synaptic activity.Somatic subthreshold potentials invade the axonal compartment to considerable distances (>350 μm), whereas spread of axonal subthreshold potentials to the soma is inefficient.Ectopic spike generation is entrained by conventional synaptic signalling mechanisms. Excitatory synaptic potentials promote EAPs, whereas inhibitory synaptic potentials block EAPs.The modulation of ectopic excitability depends on propagation of somatic voltage deflections to the axonal EAP initiation site.Synaptic modulation of EAP initiation challenges the view of the distal axon being independent of synaptic activity and may contribute to mechanisms underlying fast network oscillations and pathological network activity. [ABSTRACT FROM AUTHOR]

Coherence between electromyographic (EMG) signals is often used to infer the common synaptic input to populations of motor neurons. This analysis, however, may be limited due to the filtering effect of the motor unit action potential waveforms. This study investigated the ability of surface EMG-EMG coherence to predict common synaptic input to motor neurons. Surface and intramuscular EMG were recorded from two locations of the tibialis anterior muscle during steady ankle dorsiflexions at 5 and 10% of the maximal force in 10 healthy individuals. The intramuscular EMG signals were decomposed to identify single motor unit spike trains. For each trial, the strength of the common input in different frequency bands was estimated from the coherence between two cumulative spike trains, generated from sets of single motor unit spike trains (reference measure). These coherence values were compared with those obtained from the coherence between the surface EMG signals (raw, rectified, and high-passed filtered at 250 Hz before rectification) using linear regression. Overall, the high-pass filtering of the EMG prior to rectification did not substantially change the results with respect to rectification only. For both signals, the correlation of EMG coherence with motor unit coherence was strong at 5% MVC (r2 > 0.8; p < 0.01), but only for frequencies > 5 Hz. At 10% MVC, the correlation between EMG and motor unit coherence was only significant for frequencies > 15 Hz (r2 > 0.8; p < 0.01). However, when using raw EMG for coherence analysis, the only significant relation with motor unit coherence was observed for the bandwidth 5-15 Hz (r2 > 0.68; p = 0.04). In all cases, there was no association between motor unit and EMG coherence for frequencies < 5 Hz (r2 ≤ 0.2; p ≥ 0.51). In addition, a substantial error in the best linear fit between motor unit and EMG coherence was always present. In conclusion, high-frequency (>5 Hz) common synaptic inputs to motor neurons can partly be estimated from the rectified surface EMG at low-level steady contractions. The results, however, suggest that this association is weakened with increasing contraction intensity and that input at lower frequencies during steady isometric contractions cannot be detected accurately by surface EMG coherence. [ABSTRACT FROM AUTHOR]