Estimating the time course of population excitatory postsynaptic potentials in motoneurons of spastic stroke survivors

Abstract

Hu X, Suresh NL, Rymer WZ. Estimating the time course of population excitatory postsynaptic potentials in motoneurons of spastic stroke survivors. J Neurophysiol 113: 1952-1957, 2015. First published December 24, 2014 doi:10.1152/jn.00946.2014.-Hyperexcitable motoneurons are likely to contribute to muscle hypertonia after a stroke injury; however, the origins of this hyperexcitability are not clear. One possibility is that the effective duration of the Ia excitatory postsynaptic potential (EPSP) is prolonged, increasing the potential for temporal summation of EPSPs, making action potential initiation easier. Accordingly, the purpose of this study was to quantify the time course of EPSPs in motoneurons of stroke survivors. The experimental protocol, which was based on parameters derived from simulation, involved sequential subthreshold electrical stimuli delivered to the median nerve of hemispheric stroke survivors. The resulting H-reflex responses were recorded in the flexor carpi radialis muscle. H-reflex response probability was then used to quantify the time course of the underlying EPSPs in the motoneuron pool. A population EPSP was estimated based on the probability of evoking an H reflex from the second electrical stimulus in the absence of a reflex response to the first stimulus. The accuracy of this time-course estimate was quantified using a computer simulation that explored a range of feasible EPSP parameters. Our experimental results showed that in all five hemispheric stroke survivors the rate of decay of the population EPSP was consistently slower in spastic compared with the contralateral motoneuron pools. We propose that one potential mechanism for hyperexcitability of motoneurons in spastic stroke survivors may be linked to this prolongation of the Ia EPSP time course. Our subthreshold double-stimulation approach also provides a noninvasive tool for quantifying the time course of EPSPs in both healthy and pathological conditions. EPSP time course; stroke; spasticity; reflex; double stimulation HYPEREXCITABILITY OF SPINAL motoneurons is potentially a major contributor to muscular hypertonia after a brain injury, such as a hemispheric stroke (Katz and Rymer 1989). This hyperexcitability can be induced by a change in either the passive or active electrical properties of these neurons, which can lead to sustained voltage changes for a given synaptic current input. These abnormal voltage changes can be captured as apparent alterations in the amplitude and time course of the excitatory postsynaptic potential (EPSP), namely a larger amplitude and/or longer decay than in normal EPSPs.The amplitude and time course of the EPSP can be measured directly in reduced animal models via intracellular recordings (Fetz and Gustafsson 1983). In contrast, such EPSP properties can only be inferred indirectly in humans, based on changes in the discharge probability of single or grouped motoneurons in response to controlled afferent stimulation (Ashby and Zilm 1982;Suresh et al. 2005;Turker and Cheng 1994). There have ...

Prolonged time course of population excitatory postsynaptic potentials in motoneurons of chronic stroke survivors

“…The darker the shade, the stronger the stimulus. C: experimental setup (adapted from Hu et al 2015). EMG, electromyogram.…”

“…The stimulus current was then gradually reduced until an FCR H-reflex was visible in only~5 of 50 stimulations under the minimum current (i.e., the subthreshold current of the first conditioning stimulus). We determined previously that an~10% response probability (i.e., 7-13%) from the first conditioning stimulus ensures an accurate estimation of the population EPSP time course (Hu et al 2015). In some cases when the response probability was not~10%, the conditioning stimulus amplitude was adjusted to keep H-reflex probability constant over time.…”

“…The double-stimulation protocol was modified from our previous study (Hu et al 2015) in several key aspects, to enable a more robust and representative estimation of the time course of population EPSPs. In the previous protocol, the current strength of the second stimulus was set at a constant level for each test sequence, and the stimulus was only varied simply by changing the time delay between the initial low-intensity stimulus and the second, larger afferent stimulus.…”

“…To address this limitation in the PSTH technique, our group recently introduced an alternative approach to noninvasively estimate the time-course of decay of the massed or population EPSP, using a double-stimulation approach (Hu et al 2015). In this protocol, the first conditioning stimulus to the nerve is given to evoke a small (subthreshold) EPSP in that essentially no motoneuron discharge is triggered, and thus no AHP linked to neuron discharge occurs (Fig.…”

“…Based on the H-reflex response probability over the span of the ISI, the time course of decay of massed population EPSPs can then be estimated. Using this novel technique, we have previously shown a preliminary result that the population EPSPs in motoneurons on the spastic side has a significantly slower decay compared with the nonspastic side of hemispheric stroke survivors (Hu et al 2015).…”