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

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

SUBMITTER: Wakefield HE

PROVIDER: S-EPMC4808106 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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

Wakefield Hilary E HE Fregosi Ralph F RF Fuglevand Andrew J AJ

Journal of neurophysiology 20151223 3

The maximum firing rates of motoneurons (MNs), activated in response to synaptic drive, appear to be much lower than that elicited by current injection. It could be that the decrease in input resistance associated with increased synaptic activity (but not current injection) might blunt overall changes in membrane depolarization and thereby limit spike-frequency output. To test this idea, we recorded, in the same cells, maximal firing responses to current injection and to synaptic activation. We ...[more]

PMID: 26745245

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Project description:Oscillations in membrane potential induced by synaptic inputs and intrinsic ion channel activity play a role in regulating neuronal excitability, but the precise mechanisms underlying their contributions remain largely unknown. Here we used electrophysiological and modeling approaches to investigate the effects of Gaussian white noise injected currents on the membrane properties and discharge characteristics of hypoglossal (HG) motoneurons in P16-21 day old rats. We found that the noise-induced membrane potential oscillations facilitated spike initiation by hyperpolarizing the cells' voltage threshold by 3.1 ± 1.0 mV and reducing the recruitment current for the tonic discharges by 0.26 ± 0.1 nA, on average (n = 59). Further analysis revealed that the noise reduced both recruitment and decruitment currents by 0.26 ± 0.13 and 0.33 ± 0.1 nA, respectively, and prolonged the repetitive firing. The noise also increased the slopes of frequency-current (F-I) relationships by 1.1 ± 0.2 Hz/nA. To investigate the potential mechanisms underlying these findings, we constructed a series of HG motoneuron models based on their electrophysiological properties. The models consisted of five compartments endowed with transient sodium (NaT), delayed-rectify potassium [K(DR)], persistent sodium (NaP), calcium-activated potassium [K(AHP)], L-type calcium (CaL) and H-current channels. In general, all our experimental results could be well fitted by the models, however, a modification of standard Hodgkin-Huxley kinetics was required to reproduce the changes in the F-I relationships and the prolonged discharge firing. This modification, corresponding to the noise generated by the stochastic flicker of voltage-gated ion channels (channel flicker, CF), was an adjustable sinusoidal function added to kinetics of the channels that increased their sensitivity to subthreshold membrane potential oscillations. Models with CF added to NaP and CaL channels mimicked the noise-induced alterations of membrane properties, whereas models with CF added to NaT and K(DR) were particularly effective in reproducing the noise-induced changes for repetitive firing observed in the real motoneurons. Further analysis indicated that the modified channel kinetics enhanced NaP- and CaL-mediated inward currents thus increasing the excitability and output of HG motoneurons, whereas they produced relatively small changes in NaT and K(DR), thus balancing these two currents and triggering variability of repetitive firing. This study provided insight into the types of membrane channel mechanisms that might underlie oscillation-induced alterations of neuronal excitability and motor output in rat HG motoneurons.

Project description:PurposeTo evaluate the biomechanical profile of subcortical backup fixation (subcortical button [SB]) in anterior cruciate ligament (ACL) reconstruction as compared with a bicortical post and washer (BP) and suture anchor (SA) when used with interference screw (IS) primary fixation and to evaluate the utility of backup fixation for tibial fixation with extramedullary cortical button primary fixation.MethodsFifty composite tibias with polyester webbing-simulated graft were used to test constructs across 10 methods. Specimens were separated into the following groups (n = 5): 9-mm IS only, BP (with and without graft and IS), SB (with and without graft and IS), SA (with and without graft and IS), extramedullary suture button (with and without graft and IS), and extramedullary suture button with BP as backup fixation. Specimens were tested under cyclic loading and then loaded to failure. Maximal load at failure, displacement, and stiffness were compared.ResultsWithout a graft, the SB and BP had similar maximal loads (802.46 ± 185.18 N vs 785.67 ± 100.96 N, P = .560), and both were stronger than the SA (368.13 ± 77.26 N, P < .001). With graft and an IS, there was no significant difference in maximal load between the BP (1,461.27 ± 173.75 N), SB (1,362.46 ± 80.47 N), and SA (1,334.52 ± 195.80 N). All backup fixation groups were stronger than the control group with IS fixation only (932.91 ± 99.86 N, P < .001). There was no significant difference in outcome measures between the extramedullary suture button groups with and without the BP (failure loads of 721.39 ± 103.32 N and 718.15 ± 108.61 N, respectively).ConclusionsSubcortical backup fixation in ACL reconstruction has similar biomechanical properties to current methods and is a viable backup fixation alternative. Backup fixation methods work synergistically with IS primary fixation to strengthen the construct. There is no advantage to adding backup fixation to extramedullary button (all-inside) primary fixation when all suture strands are secured to the extramedullary button.Clinical relevanceThis study provides evidence that subcortical backup fixation is a viable alternative for surgeons during ACL reconstruction.

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

Publications

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

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