Brief Burst Of Action Potentials Research Articles

Differential contribution of TRPM4 and TRPM5 nonselective cation channels to the slow afterdepolarization in mouse prefrontal cortex neurons.

In certain neurons from different brain regions, a brief burst of action potentials can activate a slow afterdepolarization (sADP) in the presence of muscarinic acetylcholine receptor agonists. The sADP, if suprathreshold, can contribute to persistent non-accommodating firing in some of these neurons. Previous studies have characterized a Ca2+-activated non-selective cation (CAN) current (ICAN) that is thought to underlie the sADP. ICAN depends on muscarinic receptor stimulation and exhibits a dependence on neuronal activity, membrane depolarization and Ca2+-influx similar to that observed for the sADP. Despite the widespread occurrence of sADPs in neurons throughout the brain, the molecular identity of the ion channels underlying these events, as well as ICAN, remains uncertain. Here we used a combination of genetic, pharmacological and electrophysiological approaches to characterize the molecular mechanisms underlying the muscarinic receptor-dependent sADP in layer 5 pyramidal neurons of mouse prefrontal cortex. First, we confirmed that in the presence of the cholinergic agonist carbachol a brief burst of action potentials triggers a prominent sADP in these neurons. Second, we confirmed that this sADP requires activation of a PLC signaling cascade and intracellular calcium signaling. Third, we obtained direct evidence that the transient receptor potential (TRP) melastatin 5 channel (TRPM5), which is thought to function as a CAN channel in non-neural cells, contributes importantly to the sADP in the layer 5 neurons. In contrast, the closely related TRPM4 channel may play only a minor role in the sADP.

Active Dendrites under Parental Supervision

Pyramidal cell dendrites are able to produce a variety of active calcium signals in brain slices. In this issue of Neuron, Grienberger etal. (2014) investigate dendritic function in the hippocampus of live mice.

Calcium action potentials in hair cells pattern auditory neuron activity before hearing onset

We found that rat central auditory neurons fire action potentials in a precise sequence of mini-bursts prior to hearing onset. This stereotyped pattern is initiated by hair cells within the cochlea, which trigger brief bursts of action potentials in auditory neurons each time they fire a Ca2+ spike. By generating theta-like activity, hair cells may limit the influence of synaptic depression in developing auditory circuits and promote consolidation of synapses.

Identification of capsaicin-sensitive rectal mechanoreceptors activated by rectal distension in mice

Rodents detect visceral pain in response to noxious levels of rectal distension. However, the mechanoreceptors that innervate the rectum and respond to noxious levels of rectal distension have not been identified. Here, we have identified the mechanoreceptors of capsaicin-sensitive rectal afferents and characterized their properties in response to circumferential stretch of the rectal wall. We have also used the lethal spotted (ls/ls) mouse to determine whether rectal mechanoreceptors that respond to capsaicin and stretch may also develop in an aganglionic rectum that is congenitally devoid of enteric ganglia. In wild type (C57BL/6) mice, graded increases in circumferential stretch applied to isolated rectal segments activated a graded increase in firing of slowly-adapting rectal mechanoreceptors. Identical stimuli applied to the aganglionic rectum of ls/ls mice also activated similar graded increases in firing of stretch-sensitive rectal afferents. In both wild type and aganglionic rectal preparations, focal compression of the serosal surface using von Frey hairs identified mechanosensitive “hot spots,” that were associated with brief bursts of action potentials. Spritzing capsaicin (10 μM) selectively onto each identified mechanosensitive hot spot activated an all or none discharge of action potentials in 32 of 56 identified hot spots in wild type mice and 24 of 62 mechanosensitive hot spots in the aganglionic rectum of ls/ls mice. Each single unit activated by both capsaicin and circumferential stretch responded to low mechanical thresholds (1–2 g stretch). No high threshold rectal afferents were ever recorded in response to circumferential stretch. Anterograde labeling from recorded rectal afferents revealed two populations of capsaicin-sensitive mechanoreceptor that responded to stretch: one population terminated within myenteric ganglia, the other within the circular and longitudinal smooth muscle layers. In the aganglionic rectum of ls/ls mice, only the i.m. mechanoreceptors were identified. Both myenteric and i.m. mechanoreceptors could be identified by their immunoreactivity to the anti-TRPV1 antibody and the vesicular glutamate transporter, Vglut2. Myenteric mechanoreceptors had a unique morphology, consisting of smooth bulbous nodules that ramified within myenteric ganglia. In summary, the rectum of wild type mice is innervated by at least two populations of capsaicin-sensitive rectal mechanoreceptor, both of which respond to low mechanical thresholds within the innocuous range. These findings suggest that the visceral pain pathway activated by rectal distension is likely to involve low threshold rectal mechanoreceptors that are activated within the normal physiological range.

Multiple vesicle recycling pathways in central synapses and their impact on neurotransmission

Short-term synaptic depression during repetitive activity is a common property of most synapses. Multiple mechanisms contribute to this rapid depression in neurotransmission including a decrease in vesicle fusion probability, inactivation of voltage-gated Ca(2+) channels or use-dependent inhibition of release machinery by presynaptic receptors. In addition, synaptic depression can arise from a rapid reduction in the number of vesicles available for release. This reduction can be countered by two sources. One source is replenishment from a set of reserve vesicles. The second source is the reuse of vesicles that have undergone exocytosis and endocytosis. If the synaptic vesicle reuse is fast enough then it can replenish vesicles during a brief burst of action potentials and play a substantial role in regulating the rate of synaptic depression. In the last 5 years, we have examined the impact of synaptic vesicle reuse on neurotransmission using fluorescence imaging of synaptic vesicle trafficking in combination with electrophysiological detection of short-term synaptic plasticity. These studies have revealed that synaptic vesicle reuse shapes the kinetics of short-term synaptic depression in a frequency-dependent manner. In addition, synaptic vesicle recycling helps maintain the level of neurotransmission at steady state. Moreover, our studies showed that synaptic vesicle reuse is a highly plastic process as it varies widely among synapses and can adapt to changes in chronic activity levels.

Motor Unit Discharge Behavior Within Phasic Bursts From Higher Threshold Motor Units

Our recent experiments on motor unit rate coding during sinusoidal force modulation tasks has focused on motor units demonstrating continued discharge without periods of de-recruitment. As these experiments continue, we are accumulating recordings of higher threshold motor units (∼20 %MVC) that contribute brief bursts of action potentials during peaks in these isometric force-matching conditions. The PURPOSE is to describe the discharge behavior of these motor units to better our understanding of how the brief activity of higher threshold motor units contributes to the gradation of muscular force. METHODS: Using indwelling electrodes, motor unit action potentials were recorded from the first dorsal interosseous muscle of 9 subjects as they performed 6 sinusoidal isometric force matching tasks .3, .6 and .9-Hz force oscillations were centered at 20% of maximum voluntary contraction (MVC) force and had amplitude of+/−3 and 6% MVC. The number of spikes, recruitment threshold force, and minimum and peak instantaneous firing rates were computed for each burst of action potentials within a recording. RESULTS: As task frequency increased, the relationship between recruitment threshold force and the number of spikes per burst strengthened (Pearson r = −.45, -.60, -.67 at .3, .6, .9-Hz, respectively). Within bursts, there was notable presence of single occurrences of high instantaneous discharge rates (>50 pps, inter-spike interval <20 ms) resulting in a skewed distribution of peak firing rates. The median peak firing rate of motor units demonstrating phasic discharge was 19.51 pps. This is less than the firing rate observed in lower threshold motor units exhibiting sustained discharge (24.2 pps). There were trends towards increases in firing rates with increases in task amplitude and frequency (p∼.1). The minimum discharge rate within a burst increased significantly with increases in task frequency (p<05: 5.9, 7.7, 9.7 pps at .3, .6 and .9-Hz, respectively). CONCLUSION: Consecutive motor unit action potentials with atypically brief inter-pulse intervals are known to enhance muscular force output. Along with the greater force output from higher threshold motor units, we need to consider the relative contributions of these brief bursts of motor unit discharge in the overall gradation of muscular force.

Network Variability Limits Stimulus-Evoked Spike Timing Precision in Retinal Ganglion Cells

Visual, auditory, somatosensory, and olfactory stimuli generate temporally precise patterns of action potentials (spikes). It is unclear, however, how the precision of spike generation relates to the pattern and variability of synaptic input elicited by physiological stimuli. We determined how synaptic conductances evoked by light stimuli that activate the rod bipolar pathway control spike generation in three identified types of mouse retinal ganglion cells (RGCs). The relative amplitude, timing, and impact of excitatory and inhibitory input differed dramatically between On and Off RGCs. Spikes evoked by repeated somatic injection of identical light-evoked synaptic conductances were more temporally precise than those evoked by light. However, the precision of spikes evoked by conductances that varied from trial to trial was similar to that of light-evoked spikes. Thus, the rod bipolar pathway modulates different RGCs via unique combinations of synaptic input, and RGC temporal variability reflects variability in the input this circuit provides.

Presynaptic Unsilencing: Searching for a Mechanism

Nascent synaptic networks have a high incidence of silent synapses. In this issue of Neuron, Shen et al. show that a brief burst of action potentials rapidly awaken silent synapses by increasing the availability of synaptic vesicles for fusion through BDNF-triggered presynaptic actin remodeling mediated by the small GTPase Cdc42.

Electrical activity in the rectum of anaesthetized dogs

There is limited data available on the electrical activity of the rectum. An in vivo canine model was developed to record 240 extracellular electrograms simultaneously from the serosal surface of the rectum thereby enabling an off-line reconstruction of the behaviour of the electrical signals. Serosal rectal electrical activity is characterized by brief bursts of action potentials (=spikes) with a frequency of 22 cycles min(-1). High-resolution mapping of these signals revealed predominant propagation of these spikes in the longitudinal direction, originating from any site and conducted for a limited time and length before stopping spontaneously, thereby describing a patch of activity. The dimension of the patches in the longitudinal direction was significantly longer than the transversal width (13.6 vs 2.4 mm; P < 0.001). Spike propagation could occur in the aboral (46% of cases), in the oral (34%) or in both directions (20%). A bolus of betanechol (i.v., 0.5 mg kg(-1)) increased the frequency of the spikes without affecting size, shape or orientation of the patches. As in other parts of the gastrointestinal system, individual spike propagation in the rectum is limited to small areas or patches. The contractile activity of the organ could possibly reflect this underlying pattern of electrical behaviour.

Enhancement of calcium‐dependent afterpotentials in oxytocin neurons of the rat supraoptic nucleus during lactation

The firing pattern of oxytocin (OT) hormone synthesizing neurons changes dramatically immediately before each milk ejection, when a brief burst of action potentials is discharged. OT neurons possess intrinsic currents that would modulate this burst. Our previous studies showed the amplitude of the Ca2+ -dependent afterhyperpolarization (AHP) following spike trains is significantly larger during lactation. In the present study we sought to determine which component of the AHP is enhanced, and whether the enhancement could be related to changes in whole-cell Ca2+ current or the Ca2+ transient in identified OT or vasopressin (VP) neurons during lactation. We confirmed, with whole-cell current-clamp recordings, our previous finding from sharp electrodes that the size of the AHP following spike trains increased in OT, but not VP neurons during lactation. We then determined that an apamin-sensitive medium-duration AHP (mAHP) and an apamin-insensitive slow AHP (sAHP) were specifically increased in OT neurons. Simultaneous Ca2+ imaging revealed that the peak change in somatic [Ca2+]i was not altered in either cell type, but the slow decay of the Ca2+ transient was faster in both cell types during lactation. In voltage clamp, the whole-cell, Ca2+ current was slightly larger during lactation in OT cells only, but current density was unchanged when corrected for somatic hypertrophy. The currents, ImAHP and IsAHP, also were increased in OT neurons only, but only the apamin-sensitive ImAHP showed an increase in current density after adjusting for somatic hypertrophy. These findings suggest a specific modulation (e.g. increased number) of the small-conductance Ca2+ -dependent K+ (SK) channels, or their interaction with Ca2+, underlies the increased mAHP/ImAHP during lactation. This larger mAHP may be necessary to limit the explosive bursts during milk ejection.

High-frequency stimulation of the subthalamic nucleus silences subthalamic neurons: a possible cellular mechanism in Parkinson’s disease

The subthalamic nucleus participates in the control of movement and is considered a surgical target in the treatment of parkinsonian symptoms. Using the rat brain in vitro slice technique we show that sustained high-frequency (>100 Hz) electrical stimulation (i.e., ‘tetanic stimulation’) of the nucleus, as used in humans to treat Parkinson’s disease, silenced subthalamic neurons. Two main cell types were identified. ‘Tonic cells’ (68%) showed delayed inward rectification, fired continuously, switched to bursting and stopped firing when strongly depolarized with injected current. Tetanic stimulation of the nucleus induced a steady depolarization (≈18 mV) that triggered action potentials at a high rate followed by bursts and finally (≈25 s) totally silenced tonic cells. The control tonic activity was recovered rapidly (<10 s) after ending stimulation. ‘Phasic cells’ (25%) discharged a single initial brief burst of action potentials both when depolarized by prolonged current injection and tetanic stimulation and did not show inward rectification. An infrequent cell type called ‘phasic–tonic’ (7%) showed a mixed discharge. We suggest that the silencing effect of tetanic stimulation is not a frequency-dependent presynaptic depression and could result from the gradual inactivation of Na +-mediated action potentials. These findings suggest that the remission of parkinsonian symptoms by treatment with high-frequency electrical stimulation of the subthalamic nucleus in humans may primarily reside on its capacity to suppress the action potential activity of subthalamic neurons.

Electrophysiological and morphological properties of cell types in the chick neostriatum caudolaterale

The neostriatum caudolaterale, in the chick also referred to as dorsocaudal neostriatal complex, is a polymodal associative area in the forebrain of birds that is involved in sensorimotor integration and memory processes. We have used whole-cell patch-clamp recordings in chick brain slices to characterize the principal cell types of the neostriatum caudolaterale. Electrophysiological properties distinguished four classes of neurons. The morphological characteristics of these classes were examined by intracellular injection of Lucifer Yellow. Type I neurons characteristically fired a brief burst of action potentials. Morphologically, type I neurons had large somata and thick dendrites with many spines. Type II neurons were characterized by a repetitive firing pattern with conspicuous frequency adaptation. Type II neurons also had large somata and thick dendrites with many spines. There was no clear morphological distinction between type I and type II neurons. Type III neurons showed high-frequency firing with little accommodation and a prominent time-dependent inward rectification. They had thin, sparsely spiny dendrites and extensive local axonal arborizations. Electrophysiological and morphological properties indicated them as being interneurons. Type IV neurons had a longer action potential duration, a larger input resistance, and a longer membrane time constant than the other classes. Type IV neurons had small somata and short dendrites with few spines. The long axon collaterals of neurons in all spiny cell classes (types I, II, IV) followed similar patterns, suggesting that neurons from all these types can contribute to the projections of the neostriatum caudolaterale to sensory, limbic and motor areas. The electrophysiological and anatomical characterization of the major classes of neurons in the caudal forebrain of the chick provides a framework for the investigation of sensorimotor integration and learning at the cellular level in birds.

Spike Frequency Decoding and Autonomous Activation of Ca2+–Calmodulin-Dependent Protein Kinase II in Dorsal Root Ganglion Neurons

Autonomous activation of calcium-calmodulin kinase (CaMKII) has been proposed as a molecular mechanism for decoding Ca(2+) spike frequencies resulting from action potential firing, but this has not been investigated in intact neurons. This was studied in mouse DRG neurons in culture using confocal measurements of [Ca(2+)](i) and biochemical measurements of CaMKII autophosphorylation and autonomous activity. Using electrical stimulation at different frequencies, we find that CaMKII autonomous activity reached near maximal levels after approximately 45 impulses, regardless of firing frequency (1-10 Hz), and autonomous activity declined with prolonged stimulation. Frequency-dependent activation of CaMKII was limited to spike frequencies in the range of 0.1-1 Hz, despite marked increases in [Ca(2+)](i) at higher frequencies (1-30 Hz). The high levels of autonomous activity measured before stimulation and the relatively long duration of Ca(2+) spikes induced by action potentials ( approximately 300 msec) are consistent with the lower frequency range of action potential decoding by CaMKII. The high autonomous activity under basal conditions was associated with extracellular [Ca(2+)], independently from changes in [Ca(2+)](i), and unrelated to synaptic or spontaneous impulse activity. CaMKII autonomous activity in response to brief bursts of action potentials correlated better with the frequency of Ca(2+) transients than with the concentration of [Ca(2+)](i). In conclusion, CaMKII may decode frequency-modulated responses between 0.1 and 1 Hz in these neurons, but other mechanisms may be required to decode higher frequencies. Alternatively, CaMKII may mediate high-frequency responses in subcellular microdomains in which the enzyme is maintained at a low level of autonomous activity or the Ca(2+) transients have faster kinetics.

Adaptation of guinea-pig vagal airway afferent neurones to mechanical stimulation.

1. Intracellular and extracellular electrophysiological recording techniques were employed to examine the mechanisms involved in adaptation of guinea-pig airway sensory neurones to suprathreshold mechanical stimulation in vitro. Extracellular recordings performed using an in vitro airway preparation revealed two unambiguously distinct subsets of mechanically sensitive nerve endings in the trachea/bronchus. In one group of fibres, the mechanical stimulus caused a brief burst of action potentials, after which the nerve rapidly adapted. In the other group of fibres, repetitive action potentials were evoked as long as the stimulus was maintained above threshold. 2. The adaptation response strictly correlated with ganglionic origin of the soma. Those fibres derived from the nodose ganglion adapted rapidly, whereas those derived from the jugular ganglion were slowly or non-adapting. 3. Intracellular recordings from airway-identified neurones in isolated intact ganglia revealed that the majority of neurones within either the nodose or jugular ganglion adapted rapidly to prolonged suprathreshold depolarizing current injections. 4. The electrophysiological adaptation of nodose ganglion-derived neurones following prolonged suprathreshold current steps was greatly reduced by 4-aminopyridine. However, 4-aminopyridine did not affect the adaptation of rapidly adapting nodose ganglion-derived nerve endings in response to mechanical stimuli. 5. The data suggest that ganglionic origin dictates adaptive characteristics of guinea-pig tracheal and mainstem bronchial afferent neurones in response to mechanical stimulation. Also, the rapid adaptation of nodose nerve endings in the trachea observed during a mechanical stimulus does not appear to be related to the adaptation observed at the soma during prolonged suprathreshold depolarizing current injections.

Activity-induced potentiation of developing neuromuscular synapses.

Electrical activity plays a critical role in shaping the structure and function of synaptic connections in the nervous system. In Xenopus nerve-muscle cultures, a brief burst of action potentials in the presynaptic neuron induced a persistent potentiation of neuromuscular synapses that exhibit immature synaptic functions. Induction of potentiation required an elevation of postsynaptic Ca2+ and expression of potentiation appeared to involve an increased probability of transmitter secretion from the presynaptic nerve terminal. Thus, activity-dependent persistent synaptic enhancement may reflect properties characteristic of immature synaptic connections, and bursting activity in developing spinal neurons may promote functional maturation of the neuromuscular synapse.

Electrical characteristics and responses to jejunal distension of neurons in Remak's juxta-jejunal ganglia of the domestic fowl.

1. Remak's nerve is a ganglionated nerve trunk found only in birds that runs parallel to the gut from the duodenal-jejunal junction to the cloaca. We report the first electrophysiological characterization of these neurons and their responses to gut distension. 2. A segment of chicken jejunum with attached Remak's nerve was pinned in an electrophysiological chamber. Neurons in Remak's ganglia were impaled with microelectrodes. The adjacent segment of gut was distended with fluid. 3. One hundred and thirty neurons were characterized into three electrophysiological classes: (i) tonic neurons (74%) fired action potentials spontaneously (frequency 3.5 Hz) and continuously (up to 40 Hz) throughout a depolarizing current pulse; (ii) AD neurons (22%) fired a brief burst of action potentials (1-10), which were followed by a prolonged after-depolarization (AD) of duration 2.8 +/- 0.3 s; and (iii) phasic neurons (4%) fired an initial burst of action potentials followed by an after-hyperpolarization (duration, 520.0 +/- 32.0 ms). Tetrodotoxin (1 microM) abolished action potentials in tonic and AD neurons as well as the after-depolarization. 4. Spontaneous fast excitatory postsynaptic potentials (FEPSPs) occurred in all classes of neurons; they were not observed, however, in ganglia isolated from the jejunum. 5. Intracellular injection of biocytin revealed that neurons could be characterized into four morphological classes. Tonic neurons, which had long and extensive dendritic trees, were Remak's Type I, II and IV neurons. AD neurons also comprised Remak's type II neurons. Phasic neurons were Remak's Type III neurons. Most neurons had axons that projected orally along Remak's nerve. 6. Distension of the jejunum evoked FEPSPs and action potentials in tonic neurons, and repetitive bursts of action potentials (1-4) followed by an after-depolarization in AD neurons. All responses to distension were blocked by hexamethonium (300 microM) and tetrodotoxin (1 microM). 7. In conclusion, neurons in Remak's juxta-jejunal nerve appear to regulate gut motility. Three distinct electrophysiological classes of neurons were observed, all of which appear to be activated by distension sensitive cholinergic intestinofugal neurons in the jejunum.

Mechanism of synchronized Ca 2+ oscillations in cortical neurons

Dissociated rat cortical neurons reassociate in vitro to form synaptically connected networks. Removal of Mg 2+ from the extracellular medium then induces neurons in the network to undergo synchronized oscillations of cytoplasmic calcium. Previous studies have shown that these calcium oscillations involve the activation of NMDA receptors and that the rising phase of each calcium spike is coincident with a brief burst of action potentials (Robinson et al., Jpn. J. Physiol. 43 (Suppl. 1) (1993) S125–130; Robinson et al., J. Neurophysiol. 70 (1993) 1606–1616; Murphy et al., J. Neurosci. 12 (1992) 4834–4845). We have found that these calcium oscillations are dependent on an influx of extracellular calcium but are independent of mobilization of calcium from intracellular stores. The influx of extracellular Ca 2+ occurs primarily through L-type voltage-gated calcium channels (VGCCs), since diltiazem inhibits calcium oscillations under all conditions. On the other hand, N-, P/Q-, and T-type VGCCs are not required for calcium oscillations, although inhibitors of these channels may act as partial antagonists. In addition to removal of Mg 2+, oscillations can also be induced by the inhibition of voltage-gated K + channels with 4-aminopyridine (4-AP), a treatment known to increase neurotransmitter release. In the presence of 4-AP, synchronized calcium oscillations become independent of NMDA receptor activation, although they continue to require activation of AMPA/KA receptors. A model for the mechanism of neuronal calcium oscillations and the reason for their synchrony is presented.

Influence of the mucosa on the excitability of myenteric neurons.

Intracellular microelectrodes were used to examine the active and passive membrane properties of neurons in the myenteric plexus of the guinea-pig small intestine. Neurons of two types were examined: S neurons, which have prominent fast excitatory postsynaptic potentials and in which action potentials are not followed by long-lasting afterhyperpolarizations, and AH neurons, which have long-lasting afterhyperpolarizations following soma action potentials. In preparations in which the myenteric ganglia and longitudinal muscle, but no mucosa, were present, most S neurons (59/64) responded to intracellular depolarizing current with brief bursts of action potentials. Regardless of the strength of a depolarizing current of 500-ms duration, these neurons never fired action potentials beyond the first 250 ms. S neurons in this state were called rapidly accommodating. In contrast, within 600 microm circumferential to the intact mucosa, 26/58 S neurons fired action potentials for most or all of the period of a 500-ms insightful depolarizing pulse. S neurons in this state were called slowly accommodating. Depolarization of S neurons in the rapidly accommodating state caused a rapidly developing reduction in membrane resistance (outward rectification; onset about 7 ms). This rectification was absent from S neurons in the slowly accommodating state. Tetraethylammonium blocked the early rectification and the changed neuronal state from rapidly accommodating to slowly accommodating. Application of tetrodotoxin to neurons in the slowly accommodating state revealed the early rectification, indicating that its absence from these neurons before tetrodotoxin was applied had been due to ongoing activity in axons providing synaptic input to the neurons. After the mucosa was disconnected from the other layers and laid back in its original position, all S neurons close to the mucosa were in the rapidly accommodating state (17/17). Slow excitatory postsynaptic potentials, evoked by electrical stimulation of nerve tracts, converted 17 of 43 S neurons from rapidly accommodating to slowly accommodating and eliminated the early outward rectification in these neurons. These results indicate that the action potential firing properties of S neurons can be changed by external influences, including the activity of synaptic inputs that release a slowly acting transmitter. Spontaneous antidromic action potentials were recorded in 8/62 AH neurons within 600 microm circumferential to the intact mucosa. It is concluded that, when the mucosa is intact, a background firing of sensory neurons occurs which leads to a state change in many S neurons innervated by the active sensory neurons. We conclude that this state change is caused by the block of a voltage-sensitive outward rectification.

The burst-like firing of spinal neurons in rats with peripheral inflammation is reduced by an antagonist of N-methyl-D-aspartate.

Ankle inflammation was induced in rats by subcutaneous injection of complete Freund's adjuvant and the firing properties of spinal neurons receiving afferent input from the inflamed areas were studied four to six days later. Comparable neurons in normal rats were also studied. In normal animals the response of neurons to ankle compression consisted of a brief burst of action potentials followed by sustained firing during stimulus application. On cessation of the stimulus there was no prolonged afterdischarge. In rats with an inflamed ankle, compression of the ankle produced firing while the stimulus was applied, but with 17 of 22 neurons there was a prolonged (219 +/- 55 s) post-stimulus afterdischarge. All neurons studied in rats with peripheral inflammation fired with intermittent bursts of action potentials, particularly during the afterdischarge and spontaneous firing. The N-methyl-D-aspartate receptor antagonist DL-2-amino-5-phosphonopentanoate was ejected microiontophoretically near the cells studied. The major effect was a near abolition of bursts present in spontaneous firing and post-stimulus afterdischarges with a lesser reduction in firing during stimulus application. Effects on afterdischarge duration were variable. Since firing in bursts is known to increase transmitter release at some sites in the brain, it is proposed that when the relevant spinal neurons fire in bursts, additional intraspinal pathways are recruited and this contributes to the expanded receptive fields of neurons and possibly to the enhanced pain experienced by manipulation of inflamed peripheral tissues.

The burst-like firing of spinal neurons in rats with peripheral inflammation is reduced by an antagonist of N-methyl-?-aspartate

Ankle inflammation was induced in rats by subcutaneous injection of complete Freund's adjuvant and the firing properties of spinal neurons receiving afferent input from the inflamed areas were studied four to six days later. Comparable neurons in normal rats were also studied. In normal animals the response of neurons to ankle compression consisted of a brief burst of action potentials followed by sustained firing during stimulus application. On cessation of the stimulus there was no prolonged afterdischarge. In rats with an inflamed ankle, compression of the ankle produced firing while the stimulus was applied, but with 17 of 22 neurons there was a prolonged (219 +/- 55 s) post-stimulus afterdischarge. All neurons studied in rats with peripheral inflammation fired with intermittent bursts of action potentials, particularly during the afterdischarge and spontaneous firing. The N-methyl-D-aspartate receptor antagonist DL-2-amino-5-phosphonopentanoate was ejected microiontophoretically near the cells studied. The major effect was a near abolition of bursts present in spontaneous firing and post-stimulus afterdischarges with a lesser reduction in firing during stimulus application. Effects on afterdischarge duration were variable. Since firing in bursts is known to increase transmitter release at some sites in the brain, it is proposed that when the relevant spinal neurons fire in bursts, additional intraspinal pathways are recruited and this contributes to the expanded receptive fields of neurons and possibly to the enhanced pain experienced by manipulation of inflamed peripheral tissues.