Plateau Potentials In Motoneurons Research Articles

Motoneuron model of self-sustained firing after spinal cord injury.

Under many conditions spinal motoneurons produce plateau potentials, resulting in self-sustained firing and providing a mechanism for translating short-lasting synaptic inputs into long-lasting motor output. During the acute-stage of spinal cord injury (SCI), the endogenous ability to generate plateaus is lost; however, during the chronic-stage of SCI, plateau potentials reappear with prolonged self-sustained firing that has been implicated in the development of spasticity. In this work, we extend previous modeling studies to systematically investigate the mechanisms underlying the generation of plateau potentials in motoneurons, including the influences of specific ionic currents, the morphological characteristics of the soma and dendrite, and the interactions between persistent inward currents and synaptic input. In particular, the goal of these computational studies is to explore the possible interactions between morphological and electrophysiological changes that occur after incomplete SCI. Model results predict that some of the morphological changes generally associated with the chronic-stage for some types of spinal cord injuries can cause a decrease in self-sustained firing. This and other computational results presented here suggest that the observed increases in self-sustained firing following some types of SCI may occur mainly due to changes in membrane conductances and changes in synaptic activity, particularly changes in the strength and timing of inhibition.

Take Your PIC: Motoneuronal Persistent Inward Currents May Be Somatic as Well as Dendritic. Focus on “Facilitation of Somatic Calcium Channels Can Evoke Prolonged Tail Currents in Rat Hypoglossal Motoneurons”

Inputs to motoneurons can be amplified and prolonged by noninactivating conductances mediating “persistent inward currents” or PICs. These currents, first identified by [Schwindt and Crill (1977)][1], are generated through voltage-dependent channels that have been thought to be confined to the

Roles of ryanodine and inositol triphosphate receptors in regulation of plateau potentials in turtle spinal motoneurons

Generation of plateau potentials in spinal motoneurons depends on activation of voltage sensitive L-type Ca 2+ channels. These channels are facilitated by metabotropic receptors known to promote release of Ca 2+ from intracellular stores. The aim of this study is to determine if Ca 2+-release receptors in the endoplasmic reticulum (ER) that are sensitive to ryanodine (RyRs) and to inositol triphosphate receptors (IP 3Rs) contribute to the generation of plateau potentials. The effects of antagonists to RyRs, IP 3Rs and phospholipase C (PLC) were tested on discharge patterns associated with plateau potentials in motoneurons in slices from the spinal cord of the turtle. Plateau-related discharge patterns, un-facilitated or facilitated by agonists for group I glutamate metabotropic receptors, muscarine-sensitive cholinergic receptors or L-type Ca 2+ channels were inhibited by blockade of RyRs. In contrast, antagonists of IP 3Rs or PLC preferentially inhibited plateau-related discharge patterns when facilitated by activation of metabotropic receptors but in only half of the cells when promoted in the absence of metabotropic facilitators. Our findings show that RyRs and IP 3Rs regulate the generation of plateau potentials in motoneurons and suggest that RyRs may be directly involved with activation of the plateau potential.

Subcellular distribution of L-type Ca2+ channels responsible for plateau potentials in motoneurons from the lumbar spinal cord of the turtle.

L-type calcium channels mediate the persistent inward current underlying plateau potentials in spinal motoneurons. Electrophysiological analysis shows that plateau potentials are generated by a persistent inward current mediated by low threshold L-type calcium channels located in the dendrites. As motoneurons express L-type calcium channels of the CaV1.2 and CaV1.3 subtypes, we have investigated the subcellular distribution of these channels using antibody labelling. The plateau generating a persistent inward current is modulated by the activation of metabotropic receptors. For this reason, we also examined the relationship between CaV1.2 and CaV1.3 subunits in motoneurons and presynaptic terminals labelled with antibodies against synapsin 1a. Motoneurons in the spinal cord of the adult turtle were identified as large neurons, immunopositive for choline acetyltransferase, located in the ventral horn. In these neurons, CaV1.2 subunits were present in the cell bodies and axons. Patches of CaV1.3 subunits were seen in association with the cell membrane of the somata and both the proximal and distal dendrites. Double labelling with an antibody against synapsin 1a showed that CaV1.3 subunits, but not CaV1.2 subunits, were always located at synaptic sites. The distribution of CaV1.2 and CaV1.3 strongly suggests that the persistent inward current underlying plateau potentials in spinal motoneurons is mediated by CaV1.3 and not by CaV1.2. Our findings also show that CaV1.3 may be located in the somatic and dendritic membrane adjacent to particular presynaptic terminals.

Sustained contractions produced by plateau-like behaviour in human motoneurones.

Electrical stimulation over human muscle can generate force directly by activation of motor axons and indirectly by 'reflex' recruitment of spinal motoneurones. These experiments were designed to define the properties of the centrally generated 'reflex' force, including the optimal stimulus conditions for producing it in tibialis anterior (TA) and triceps surae (TS), and its interaction with volition. Subjects (n = 21) were seated with their foot strapped to an isometric myograph. Surface EMG was recorded from TS and TA. High-frequency electrical stimulation (100 Hz) of TS and TA with wide pulse widths (1 ms) was most effective to evoke the sustained centrally generated forces. The maximal force evoked by this mechanism during stimulation of TA for 40 s was approximately 42 % of that produced by a maximal voluntary contraction. For both muscle groups, ramp increases and decreases in stimulus frequency (from approximately 4 to 100 Hz and back to 4 Hz over 6 s) resulted in marked hysteresis in the force-frequency plot. After a single 'burst' of 100 Hz stimulation during prolonged stimulation at 25 Hz, force remained elevated. Repeated bursts often generated progressively larger force increments. These behaviours were abolished by an anaesthetic nerve block proximal to the stimulation site, confirming the central origin for the 'extra' force. After a brief voluntary contraction was performed during 25 Hz stimulation, force remained elevated, and this showed some gradation with voluntary contraction amplitude. Sometimes voluntary contractions alone initiated the sustained central motor output. Involuntary contractions often persisted for many seconds after electrical stimulation ceased. These were not terminated by brief inhibitory inputs to the active motoneurones but could be stopped by the voluntary command to 'relax completely'. Overall, these centrally generated contractions are consistent with activation of plateau potentials in motoneurones innervating the ankle dorsiflexors and plantarflexors. Large forces can be produced through this mechanism. The interaction with volitional drives suggests that plateau behaviour may contribute significantly to the normal output of human motoneurones.

Facilitation of plateau potentials in turtle motoneurones by a pathway dependent on calcium and calmodulin.

1. The involvement of intracellular calcium and calmodulin in the modulation of plateau potentials in motoneurones was investigated using intracellular recordings from a spinal cord slice preparation. 2. Chelation of intracellular calcium with BAPTA-AM or inactivation of calmodulin with W-7 or trifluoperazine reduced the amplitude of depolarization-induced plateau potentials. Inactivation of calmodulin also inhibited facilitation of plateau potentials by activation of group I metabotropic glutamate receptors or muscarinic receptors. 3. In low-sodium medium and in the presence of tetraethylammonium and tetrodotoxin, calcium action potentials evoked by depolarization were followed by a short hyperpolarization ascribed to the calcium-activated non-selective cationic current (ICAN) and by a dihydropyridine-sensitive afterdepolarization. The amplitude of the afterdepolarization depended on the number of calcium spikes and was mediated by L-type calcium channels. 4. The dihydropyridine-sensitive afterdepolarization induced by calcium spikes was reduced by blockade of calmodulin. 5. It is proposed that plateau potentials in spinal motoneurones are facilitated by activation of a calcium-calmodulin-dependent pathway.

Chapter 21 Possible functions of transmitter-controlled plateau potentials in α motoneurones

An increasing number of vertebrate central neurones has been shown to possess complex membrane properties. However, the functional significance of such properties is unclear. The aim of the present paper is to review some old and new findings in this field from this laboratory. First, a bistability in alpha motoneurones in reduced preparations is described. Thereafter we present some new data on a bistable behaviour in motor units in unrestrained intact animals during posture. Finally, the possible role of motoneuronal bistability in locomotion and in spasticity is discussed. Recently a bistable firing behaviour in motoneurones was described in the unanaesthetized decerebrate cat. This behaviour is generated by a plateau potential, which causes long-lasting excitability increase and can be initiated and terminated by short-lasting synaptic excitation and inhibition respectively, and is contingent upon activity in descending noradrenergic and serotonergic systems. In an in vitro preparation of the turtle spinal cord the plateau potential was shown to be serotonin dependent and generated by a voltage-dependent non-inactivating calcium conductance. In order to elucidate possible functional consequences of a bistable firing behaviour in the intact animal, the firing pattern of individual soleus motor units was studied by means of chronic EMG registration in awake unrestrained rats during quiet standing. Implanted electrodes allowed the delivery of excitatory and inhibitory stimulus trains to the motoneurones. It was found that short-lasting synaptic stimulation could induce maintained shifts between two stable levels of motoneurone firing frequencies, as in the decerebrate cat. Spontaneous shifts between the same two levels were also present. It seems most likely that plateau potentials are responsible for this bistable firing property in intact animals. The role of plateau potentials in locomotion is difficult to study. At present there are no clear indications of the utilization of plateau potentials in locomotion in intact animals. However, "clamped frequency" bursts which are observed in fictive locomotion in spinal cats might be explained by plateaus. The existence of plateau potentials in motoneurones may also be of importance in spasticity. Therefore, the development of spasticity in two spinalized cats was followed for 3 weeks. Acute experiments demonstrated plateau potentials in some motoneurones in this preparation.

Plateau potentials in alpha-motoneurones induced by intravenous injection of L-dopa and clonidine in the spinal cat.

1. Intracellular recordings were made from lumbar alpha-motoneurones in unanaesthetized decerebrate acute spinal cats. The response of motoneurones to direct current pulse injection or synaptic excitation was investigated following intravenous injection of L-beta-3,4-dihydroxyphenylalanine (L-DOPA, 20-120 mg/kg) alone, nialamide (10-50 mg/kg) and L-DOPA or clonidine (0.5-1 mg/kg). 2. The response properties of motoneurones were tested with rectangular and triangular current waveforms. Before L-DOPA treatment motoneuronal firing during a rectangular current pulse is characterized by an initial high firing frequency which rapidly decreases to a lower steady-state firing which is maintained only for the duration of the pulse. Following administration of L-DOPA an acceleration in firing frequency is apparent following the initial adaptation seen with rectangular current pulses. A transient after-depolarization or an after-discharge often followed the termination of the pulse. The frequency-current relation in response to a triangular current injection changed from a clockwise to a counter-clockwise hysteresis after L-DOPA treatment (i.e. after L-DOPA the firing frequency was higher for any given current during the descending phase than during the ascending phase of the triangular waveform). 3. Firing acceleration during and self-sustained firing after rectangular current pulses and counter-clockwise hysteresis of firing frequency with triangular current pulses are causally related to the presence of plateau potentials, which can be directly visualized after inactivation of the spikes. Plateau potentials in motoneurones could be generated by short-lasting intracellular depolarizing current pulses or brief excitatory synaptic inputs and terminated by short-lasting hyperpolarizing current pulses or brief inhibitory synaptic inputs. Plateau potentials were demonstrated in flexor and extensor motoneurones. 4. All bistable properties described in the preceding paragraphs following L-DOPA administration could also be seen after administration of the alpha-receptor agonist clonidine. 5. Slow rhythmic oscillations of the membrane potential (7.5-10 Hz) were seen superimposed on plateau potentials in a few cells after administration of L-DOPA and clonidine. The oscillations had an amplitude in the range 10-20 mV and represent the expression of an intrinsic property of the motoneurone. 6. It is demonstrated that plateau potentials in the motoneurones contribute to the late long-lasting reflexes observed in L-DOPA-treated spinal cats. 7. It is concluded that L-DOPA (and clonidine) change the response properties of the motoneurones in an analogous way to 5-hydroxy-DL-tryptophan (5-HTP).(ABSTRACT TRUNCATED AT 400 WORDS)

Bistability of alpha‐motoneurones in the decerebrate cat and in the acute spinal cat after intravenous 5‐hydroxytryptophan.

1. In the preceding paper (Crone, Hultborn, Kiehn, Mazieres & Wigström, 1988) it was shown that a short-lasting synaptic excitation ('on' stimulus) of extensor motoneurones (primarily triceps surae) in the decerebrate cat often resulted in a maintained excitability increase, which could be reset by a short-lasting inhibitory stimulus train ('off' stimulus). In the present experiments intracellular recording from triceps surae motoneurones and the electroneurogram (ENG activity) from triceps surae nerve branches were performed in parallel. 2. Sustained firing of individual triceps surae motoneurones was most often recorded in parallel with the maintained ENG activity following a synaptic 'on' stimulus. When the motoneurone was silenced, by a hyperpolarizing current through the microelectrode, there was no sign of on-going synaptic excitation during the maintained ENG activity following an 'on' stimulus. It was therefore suggested that voltage-dependent intrinsic properties of the motoneurones themselves could be responsible for the maintained firing. 3. In confirmation of this hypothesis it was found that short-lasting depolarizing current pulses through the recording microelectrode could trigger a self-sustained firing in the motoneurone provided that the bias current (i.e. the holding potential) was kept within certain limits. Hyperpolarizing current pulses terminated the firing. When the spike-generating mechanism was inactivated (by long-lasting excessive depolarization) similar depolarizing and hyperpolarizing current pulses could initiate and terminate plateau potentials in the motoneurones. By grading the depolarizing current pulses it was found that the plateau potentials were of all-or-none character, typically around 10 mV in amplitude. The two levels of excitability which can be triggered by short-lasting excitation and inhibition of the motoneurones is referred to as 'bistable' behaviour of the motoneurones. 4. After an acute spinal transection, in the unanaesthetized cat, the bistable behaviour of the motoneurones disappeared. However, it reappears following intravenous injection of the serotonin precursor 5-hydroxytryptophan (50-120 mg/kg). 5. Individual triceps surae motor units were recorded by selective EMG electrodes during tonic stretch reflexes in the decerebrate preparations. Based on an analysis of their firing pattern during lengthening and shortening (or vibration) of the muscle it is suggested that plateau potentials in motoneurones are recruited during the tonic stretch reflex. Furthermore, it is argued that a quantitatively important part of the depolarization of motoneurones during the tonic stretch reflex indeed originates from these plateau potentials.(ABSTRACT TRUNCATED AT 400 WORDS)

Electrophysiological signs of recovery after experimentally produced ischemia and hypoglycemia in the rat : I. Rosén, S. Rehncrona, C.D. Agardh and B. Siesjö (Lund, Sweden)

An increasing number of vertebrate central neurones has been shown to possess complex membrane properties. However, the functional significance of such properties is unclear. The aim of the present paper is to review some old and new findings in this field from this laboratory. First, a bistability in α motoneurones in reduced preparations is described. Thereafter we present some new data on a bistable behaviour in motor units in unrestrained intact animals during posture. Finally, the possible role of motoneuronal bistability in locomotion and in spasticity is discussed. Recently a bistable firing behaviour in motoneurones was described in the unanaesthetized decerebrate cat. This behaviour is generated by a plateau potential, which causes long-lasting excitability increase and can be initiated and terminated by short-lasting synaptic excitation and inhibition respectively, and is contingent upon activity in descending noradrenergic and serotonergic systems. In an in vitro preparation of the turtle spinal cord the plateau potential was shown to be serotonin dependent and generated by a voltage-dependent non-inactivating calcium conductance. In order to elucidate possible functional consequences of a bistable firing behaviour in the intact animal, the firing pattern of individual soleus motor units was studied by means of chronic EMG registration in awake unrestrained rats during quiet standing. Implanted electrodes allowed the delivery of excitatory and inhibitory stimulus trains to the motoneurones. It was found that short-lasting synaptic stimulation could induce maintained shifts between two stable levels of motoneurone firing frequencies, as in the decerebrate cat. Spontaneous shifts between the same two levels were also present. It seems most likely that plateau potentials are responsible for this bistable firing property in intact animals. The role of plateau potentials in locomotion is difficult to study. At present there are no clear indications of the utilization of plateau potentials in locomotion in intact animals. However, “clamped frequency” bursts which are observed in fictive locomotion in spinal cats might be explained by plateaus. The existence of plateau potentials in motoneurones may also be of importance in spasticity. Therefore, the development of spasticity in two spinalized cats was followed for 3 weeks. Acute experiments demonstrated plateau potentials in some motoneurones in this preparation.