An M-like outward current regulates the excitability of spinal motoneurones in the adult turtle

Alaburda, Aidas; Perrier, Jean‐François; Hounsgaard, Jørn

doi:10.1111/j.1469-7793.2002.00875.x

Cited by 27 publications

(46 citation statements)

References 3 publications

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“…On the other hand, firing frequency increased in the presence of carbachol in oculomotor nucleus Mns. Similar results have been reported in other populations (Alaburda et al 2002;Brown and Yu 2000;Chevallier et al 2006;Fernández de Sevilla et al 2006;Miles et al 2007). There is general consensus that activation of muscarinic receptors produces an increase in firing frequency by diminishing calcium-dependent potassium conductance and I M current modifying AHP.…”

Section: Excitability Of Oculomotor Nucleus Mns Depends On Cholinergisupporting

confidence: 80%

“…notion that this response was attributable to the activation of cholinergic receptors of the Mns. Depolarization in response to cholinergic agonists is a common characteristic reported in hypoglossal and spinal Mns (Alaburda et al 2002;Chevallier et al 2006;Lape and Nistri 2000;Miles et al 2007) and neurons of different nuclei (Klink and Alonso 1997a,b;McQuiston and Madison 1999;Navarro-Ló pez et al 2004;Nuñ ez et al 1997;Yajeya et al 1997). Membrane depolarization has been attributed to suppression of various K ϩ currents (Krnjevic 1993), activation of Ca 2ϩ -dependent or -independent nonselective cationic conductance (Fisahn et al 2002;Honda et al 2003;Klink and Alonso 1997b;Yajeya et al 1999), and activation of the mixed Na ϩ /K ϩ current I h (Fisahn et al 2002).…”

Section: Excitability Of Oculomotor Nucleus Mns Depends On Cholinergimentioning

confidence: 99%

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Muscarinic Modulation of Recruitment Threshold and Firing Rate in Rat Oculomotor Nucleus Motoneurons

Nieto-González¹,

Carrascal²,

Nuñez-Abades³

et al. 2009

Journal of Neurophysiology

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Nieto-Gonzalez JL, Carrascal L, Nunez-Abades P, Torres B. Muscarinic modulation of recruitment threshold and firing rate in rat oculomotor nucleus motoneurons. J Neurophysiol 101: 100 -111, 2009. First published October 29, 2008 doi:10.1152/jn.90239.2008. Above recruitment threshold, ocular motoneurons (Mns) show a firing rate linearly related with eye position. Current hypothesis suggests that synaptic inputs are determinant for establishing the recruitment threshold and firing rate gain in these Mns. We investigated this proposal by studying the cholinergic modulation in oculomotor nucleus Mns by intracellular recordings in rat brain slice preparation. All recorded Mns were silent at their resting membrane potential. Bath application of carbachol (10 m) produced a depolarization and a sustained firing that was not silenced on returning membrane potential to the precarbachol value via DC injection. In response to similar membrane depolarization or equal-current steps, carbachol-exposed Mns produced a higher firing rate and a shorter spike afterhyperpolarization phase with lower amplitude. The relationship between injected current and firing rate (I-F) was linear in control and carbachol-exposed Mns. The slope of these relationships (I-F gain) decreased with carbachol exposure. Bath application of agonist and antagonist of nicotinic and muscarinic acetylcholine receptors in addition to immunohistochemical studies support the notion that muscarinic receptors are primarily involved in the preceding responses. We conclude that muscarinic inputs play an important role in determining the recruitment threshold and firing rate gain observed in oculomotor Mns in vivo.

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Section: Excitability Of Oculomotor Nucleus Mns Depends On Cholinergisupporting

confidence: 80%

Section: Excitability Of Oculomotor Nucleus Mns Depends On Cholinergimentioning

confidence: 99%

Muscarinic Modulation of Recruitment Threshold and Firing Rate in Rat Oculomotor Nucleus Motoneurons

Nieto-González¹,

Carrascal²,

Nuñez-Abades³

et al. 2009

Journal of Neurophysiology

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“…Such a current is present in turtle spinal motoneurons (Alaburda et al, 2002), and KCNQ channels, which underlie the M current, are expressed at the axon initial segment of mouse motoneurons where spikes are generated (Pan et al, 2006). The M-like current certainly plays a role in reducing the motoneurons excitability, but it cannot account for the reduction of spike amplitude.…”

Section: A Matter Of Membrane Excitabilitymentioning

confidence: 99%

Mixed Mode Oscillations in Mouse Spinal Motoneurons Arise from a Low Excitability State

Iglesias¹,

Meunier²,

Manuel³

et al. 2011

J. Neurosci.

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We explain the mechanism that elicits the mixed mode oscillations (MMOs) and the subprimary firing range that we recently discovered in mouse spinal motoneurons. In this firing regime, high-frequency subthreshold oscillations appear a few millivolts below the spike voltage threshold and precede the firing of a full blown spike. By combining intracellular recordings in vivo (including dynamic clamp experiments) in mouse spinal motoneurons and modeling, we show that the subthreshold oscillations are due to the spike currents and that MMOs appear each time the membrane is in a low excitability state. Slow kinetic processes largely contribute to this low excitability. The clockwise hysteresis in the I-F relationship, frequently observed in mouse motoneurons, is mainly due to a substantial slow inactivation of the sodium current. As a consequence, less sodium current is available for spiking. This explains why a large subprimary range with numerous oscillations is present in motoneurons displaying a clockwise hysteresis. In motoneurons whose I-F curve exhibits a counterclockwise hysteresis, it is likely that the slow inactivation operates on a shorter time scale and is substantially reduced by the de-inactivating effect of the afterhyperpolarization (AHP) current, thus resulting in a more excitable state. This accounts for the short subprimary firing range with only a few MMOs seen in these motoneurons. Our study reveals a new role for the AHP current that sets the membrane excitability level by counteracting the slow inactivation of the sodium current and allows or precludes the appearance of MMOs.

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“…The voltage-dependence of activation was taken from a recent model of the M-current in hippocampal cells (Hu et al 2009), but the kinetics of activation were made two orders of magnitude slower to mimic the outward current used by Revill and Fuglevand (2011) to produce spike frequency adaptation, which had a time constant of 22 s. Although an M-current has been reported in turtle motoneurons (Alaburda et al 2002) and KCNQ channels are present on the initial segments of mouse motoneurons (Duflocq et al 2011), there has been no report of an M-current with a time constant on the order of seconds: we have simply chosen this as a mechanism to produce a slow, outward current.…”

Section: Additional Model Mechanismsmentioning

confidence: 99%

Contribution of intrinsic motoneuron properties to discharge hysteresis and its estimation based on paired motor unit recordings: a simulation study

Powers

Heckman

2015

Journal of Neurophysiology

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Powers RK, Heckman CJ. Contribution of intrinsic motoneuron properties to discharge hysteresis and its estimation based on paired motor unit recordings: a simulation study. J Neurophysiol 114: 184 -198, 2015. First published April 22, 2015 doi:10.1152/jn.00019.2015.-Motoneuron activity is strongly influenced by the activation of persistent inward currents (PICs) mediated by voltage-gated sodium and calcium channels. However, the amount of PIC contribution to the activation of human motoneurons can only be estimated indirectly. Simultaneous recordings of pairs of motor units have been used to provide an estimate of the PIC contribution by using the firing rate of the lower threshold unit to provide an estimate of the common synaptic drive to both units, and the difference in firing rate (⌬F) of this lower threshold unit at recruitment and de-recruitment of the higher threshold unit to estimate the PIC contribution to activation of the higher threshold unit. It has recently been suggested that a number of factors other than PIC can contribute to ⌬F values, including mechanisms underlying spike frequency adaptation and spike threshold accommodation. In the present study, we used a set of compartmental models representing a sample of 20 motoneurons with a range of thresholds to investigate how several different intrinsic motoneuron properties can potentially contribute to variations in ⌬F values. We drove the models with linearly increasing and decreasing noisy conductance commands of different rate of rise and duration and determined the influence of different intrinsic mechanisms on discharge hysteresis (the difference in excitatory drive at recruitment and de-recruitment) and ⌬F. Our results indicate that, although other factors can contribute, variations in discharge hysteresis and ⌬F values primarily reflect the contribution of dendritic PICs to motoneuron activation.

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An M-like outward current regulates the excitability of spinal motoneurones in the adult turtle

Cited by 27 publications

References 3 publications

Muscarinic Modulation of Recruitment Threshold and Firing Rate in Rat Oculomotor Nucleus Motoneurons

Muscarinic Modulation of Recruitment Threshold and Firing Rate in Rat Oculomotor Nucleus Motoneurons

Mixed Mode Oscillations in Mouse Spinal Motoneurons Arise from a Low Excitability State

Contribution of intrinsic motoneuron properties to discharge hysteresis and its estimation based on paired motor unit recordings: a simulation study

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