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PubMed1992

Spontaneous and stimulated firing in cultured rat suprachiasmatic neurons.

Neurons from the suprachiasmatic nucleus (SCN) of the hypothalamus, the site of a circadian pacemaker in mammals, were isolated from embryonic rat. After mechanical dissociation neurons were brought into culture for 1-2 weeks, using a chemically defined medium. Recordings were made from 74 bipolar neurons using two different configurations of the patch-clamp technique. During cell attached patch recordings, 45% of neurons fired spontaneously. The mean firing rate was 0.7 +/- 0.6 Hz and the firing pattern was irregular. In whole cell recordings 73% of the investigated neurons showed spontaneous activity with an irregular firing pattern. The mean spontaneous firing rate with an intracellular Cl- concentration of 145 mM was 1.0 +/- 0.6 Hz. The resting membrane potential of the bipolar neurons was estimated to be -62 +/- 24 mV. An intracellular Cl- concentration of 145 mM depolarised the membrane potential. It also increased the probability of spontaneous firing. A depolarising current stimulus produced an action potential with a threshold voltage of -46 +/- 9 mV. Suprathreshold stimuli resulted in repetitive firing with a mean frequency of 12 +/- 4 Hz. The minimum interspike interval was 52 +/- 14 ms. All action potentials either occurring spontaneously or elicited by current stimuli were abolished by the Na(+)-channel blocker TTX. These results indicate that our cultured neurons have some electrophysiological properties in common with SCN neurons in brain slices and in vivo.

Action Potentials↗
PubMed1993

Inhibition of substantia nigra dopamine cell firing by R(-)-N-n-propylnorapomorphine: electrophysiological and autoradiographic studies after regional inactivation of dopamine receptors by microinjection of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline.

The irreversible receptor inactivator, N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), was injected into rat striatum or substantia nigra to study potential contributions of dopamine receptors in each area to the inhibition of substantia nigra (A9) dopamine cell firing by i.v. R(-)-N-n-propylnorapomorphine (NPA), a dopamine agonist. Extracellular, single unit recording studies showed that the numbers of active dopamine cells, basal firing rates and responses to i.v. R(-)-NPA were unchanged a day after striatal EEDQ injections, despite significant losses of striatal D1 and D2 receptors (confirmed by autoradiography). These results indicate that striatal receptors do not control the basal activity of A9 neurons, nor do they mediate inhibitions of firing by R(-)-NPA. Microinjections of EEDQ into substantia nigra, however, inactivated 75-78% of nigral D1 and D2 receptors and reduced the number of active dopamine cells and slightly increased firing rates. Moreover, dose-response curves to R(-)-NPA were shifted 10-fold to the right and the maximum inhibitory response was depressed. Furchgott analysis of the dose-response curves yielded a steep occupancy-response curve with maximum (> 95%) inhibition of firing at only 24% receptor occupation (i.e., 76% reserve). Thus, the substantial (approximately 70%) receptor reserve previously shown to exist for inhibition of dopamine cell firing by i.v. R(-)-NPA20,21 appears to be intrinsic to the nigra. To assess contributions of nigral D1 and D2 receptors to this response, selective inactivation of each receptor subtype was achieved (confirmed autoradiographically) by treating rats with SCH 23390 (4 mg/kg) or S(-)eticlopride (2 mg/kg), respectively, 30 min before intranigral EEDQ. Selective D2, but not D1, receptor inactivation produced rightward shifts and depressed the maximum of the R(-)-NPA dose-response curve in a manner like that observed after non-selective inactivation of nigral dopamine receptors. Unexpectedly, pretreatment with SCH 23390 (to protect D1 receptors) also produced a modest rightward shift in the R(-)-NPA dose-response curve, suggesting a slight role for D1 receptors in this response. These results indicate that inhibition of A9 dopamine cell firing by i.v. R(-)-NPA is mediated by dopamine receptors located in substantia nigra, but not striatum and confirm the predominant role of nigral D2 receptors.

Action Potentials↗
PubMed1988

Excitability of firing motoneurones tested by Ia afferent volleys in human triceps surae.

The excitability of a firing human motoneurone was tested by Ia afferent excitatory volleys. An H reflex was evoked by stimulation of the tibial nerve while the subjects maintained the background rhythmic firing of single MU of the soleus and of the medialis gastrocnemius during weak voluntary contraction. The mean background firing rate of MUs ranged from 3.6 to 9.4 imp/sec. In order to estimate the 'effectiveness' of an afferent volley, PSTHs were constructed. The firing index was used as a measure of motoneurone excitability. It has been shown that the 'effectiveness' of an afferent volley decreases with an increase in background firing rate of a MU. Such a dependence was deduced from changes in current motoneurone excitability within an interspike interval. The results indicate that during natural muscle contraction at a low firing rate of a motoneurone, the discharge rate is one of the factors affecting the excitability of a firing motoneurone and, hence, its input-output relations. The method of testing changes in human motoneurone excitability within an interspike interval may prove useful in studies on interaction of volleys arriving at a motoneurone via different excitatory inputs.

Afferent Pathways↗
PubMed1990

Testing excitability of human motoneurones capable of firing double discharges.

Single motor unit (MU) action potentials were recorded from the flexor carpi ulnaris during its weak voluntary contraction in 6 healthy subjects. At low frequencies of motoneuronal firing (the average interspike interval ranged from 70 +/- 8 to 200 +/- 22 msec), double discharges with interspike intervals from 5 to 20 msec were seen from about one-fourth of all MUs (62 out of 249). Monosynaptic testing of the excitability of firing motoneurones was carried out to study the probable mechanism of doublets. By stimulating the ulnar nerve against the background of firing MUs an H-reflex was elicited. The excitability of the motoneurones was evaluated by a firing index whose changes within an interspike interval were analysed (the step width was 10 msec). The testing of 47 MUs has shown that motoneurones capable of firing double discharges during voluntary muscle contraction have a higher excitability at the beginning of an interspike interval (the first 20 msec) as compared to those incapable of firing double discharges. Our data confirm that the leading part in the formation of double discharges is played by delayed depolarization occurring in a firing motoneurone after its successive discharge. The correlation between the characteristics of doublets and the properties of delayed depolarization are discussed. It is proposed that motoneurones with a delayed depolarization possess certain transduction properties as they produce a maximal instantaneous increase in discharge frequency on a minimal increase in synaptic input. This study has revealed a phase of increased excitability in the motoneurone axon during the first 15 msec after a regular rhythmic discharge has been propagated.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1995

Effects of premotion silent period on single motor unit firing at initiation of a rapid contraction.

We compared the single motor unit (SMU) activity between movements with a premotion silent period (PMSP) and without PMSP in EMG. Fourteen SMUs in the gastrocnemius muscle and 6 SMUs in the soleus muscle were recorded from 5 volunteers during isometric plantar flexion. Tonically firing SMUs failed to fire just before the onset of a rapid contraction with PMSP more frequently than without PMSP. SMUs tended to fire within 10 msec (the gastrocnemius SMUs) or 20 msec (the soleus SMUs) from the onset of the phasic EMG discharge when PMSP occurred. In a rapid contraction without PMSP, the initial firing of SMUs occurred with longer latency than that in a rapid contraction with PMSP. The latency of the initial SMU firing in a rapid contraction related to the preceding time of the last SMU firing during a sustained contraction to the onset of the phasic EMG discharge. When the preceding firing was long enough, the latency distributed around 10 msec. On the other hand, for shorter preceding times, the latency lengthened with shortening of the preceding time. It is suggested that the PMSP makes the preceding time long and increases the susceptibility of motor units to the descending command at the initiation of a rapid contraction.

Adult↗
PubMed1991

Sources of color variation on firing porcelain.

The final color matching of porcelain crowns depends upon the accuracy of the original shade matching by the dentist and variables introduced during processing. Possible sources of processing variables include thickness and color of the opaque, thickness, color, and translucency of the body and enamel layers, firing temperature, and number of firings (Miller, 1987). These processing variables can lead to an error in shade match. The purpose of this study was to quantify, in CIE delta E units: (1) the shade variations when the same batches are fired, (2) the shade variations between different batches, and (3) the differences in color produced by the multiple firing. Three lots of six shades of four commercial brands were included in this study. The color variation of the opaque samples (mean delta E was 0.46) was generally lower than that of the body/opaque samples (mean delta E was 0.86). The average color variation for three different batches of the body/opaque samples was 1.44. The average color difference produced as a result of multiple firings was 1.00 after six firings, compared with the color after three firings.

Analysis of Variance↗
PubMed1987

Structurally stable burst and synchronized firing in human amygdala neurons: auto- and cross-correlation analyses in temporal lobe epilepsy.

Burst structure and synchronized firing of bursts were studied, in the interictal period, using auto- and cross-correlation analyses in human amygdala neurons in temporal lobe epilepsy patients diagnosed as having a unilateral limbic seizure focus in anterior hippocampus and/or amygdala. Satisfactory single unit recordings were obtained from chronically implanted microelectrodes in 51 amygdala neurons, and auto-correlation analysis identified 27 of 51 neurons where burst firings recurred with regular interspike interval structures (structurally stable burst: S-burst). This structural stability was characteristic only for a short burst, or at the beginning of a series of repetitive firings, involving 2-5 action potentials. In 'non-epileptic' amygdala neurons located contralateral to the seizure focus, the average duration of S-burst was 15 msec and the number of action potentials (spikes) in the S-burst was inversely related to the interspike intervals in the S-burst, suggesting that endogenous membrane characteristics of non-epileptic amygdala neurons determine the patterns of S-burst. In contrast, in the seizure focus amygdala ('epileptic'), the duration of the S-burst was prolonged among epileptic neurons, not because of the occurrence of more action potentials within the S-burst, but because of a prolonged interspike interval within the S-burst. Furthermore, there was no relationship between the interspike interval and the number of action potentials in the S-burst, suggesting that synaptic inputs and/or extracellular environmental factors may affect an intrinsic mechanism for generating stable S-burst in epileptic neurons. Cross-correlation analysis identified synchronized firings in epileptic neurons: when two epileptic neurons both exhibited S-bursts, when either epileptic neuron exhibited S-burst, but never when neither exhibited S-bursts. Conversely, non-epileptic neurons rarely fired synchronously; even though they showed S-bursts. The difference in the pattern of S-bursts between epileptic and non-epileptic amygdala neurons seems to be the degree of firing synchrony. Our results provide, for the first time, direct evidence that human epileptogenic amygdala neurons recorded in vivo have unique burst firing patterns and significant synchronous excitatory interactions, different from a burst pattern found in non-epileptogenic amygdala neurons during the interictal period.

Action Potentials↗
PubMed2004

Fire ant attacks on patients in nursing homes: an increasing problem.

We review the medical reports of fire ant attacks on residents of nursing homes in the context of the medical entomology of these insects, and present recommendations to prevent and manage future attacks. Two reports were recent cases, while a computer-assisted search yielded four other similar cases of attacks by foraging fire ants in the last 10 years. One patient experienced an anaphylactic reaction and 4 patients died within 1 week of the attack. Ants were usually noted in health care facilities days before the attacks. The presence of fire ants around immobile, often cognitively impaired, patients seems to be the primary risk factor for massive fire ant attacks. Health care providers and administrators in fire ant endemic areas must be aware that the presence of fire ants in hospitals and nursing homes represents a hazard. Fire ant infestation can lead to sting attacks on patients, causing respiratory tract obstruction, worsening of pre-existing medical conditions, or frank anaphylaxis. All the attacks reported here have resulted in legal action involving physicians and health care facilities.

Animals↗
PubMed2004

Detecting location-specific neuronal firing rate increases in the hippocampus of freely-moving monkeys.

The spatial properties of the firing of hippocampal neurons have mainly been studied in (a) freely moving rodents, (b) non-human primates seated in a moveable primate chair with head fixed, and (c) epileptic patients subjected to virtual navigation. Although these studies have all revealed the ability of hippocampal neurons to generate spatially selective discharges, the detected firing patterns have been found to be considerably different, even conflicting, in many respects. The present cellular electrophysiological study employed squirrel monkeys (Saimiri sciureus), which moved freely on the walls and floor of a large test chamber. This permitted the examination of the spatial firing of hippocampal neurons in nearly ideal conditions, similar to those used in rodents, yet in a species that belongs to the primate Suborder Anthropoidea. The major findings were that: (1) a group of slow-firing complex-spike cells increased their basal, awake firing rate more than 20-fold, often above 30 spikes/s, when the monkey was in a particular location in the chamber, (2) these location-specific discharges occurred consistently, forming 4-25 s action potential volleys, and (3) fast-firing cells displayed no such electrical activity. Thus, during free movement in three dimensions, primate hippocampal complex-spike cells do generate high-frequency, location-specific action potential volleys. Since these cells are components of the medial temporal lobe memory system, their uncovered firing pattern may well be involved in the formation of declarative memories on places.

Action Potentials↗
PubMed2005

Burst firing of oxytocin neurons in male rat hypothalamic slices.

Burst firing and single spike activity play different roles in the modulation of local neuronal circuit activity and neurosecretion. In hypothalamic oxytocin (OT) neurons in vivo, burst firing is associated with pulsatile secretion of OT in the milk ejection reflex, and can be observed in slices from both immature and lactating rats in vitro. Whether OT neurons from male rats also possess burst firing capability is still an open question. To examine this possibility, whole-cell patch clamp recordings were made in supraoptic nucleus OT neurons in brain slices from male rats. In low Ca(2+) medium, the alpha(1)-adrenoceptor agonist, phenylephrine evoked bursts that were highly similar to those from lactating rats in vivo and in vitro: explosive onset, short-duration, quickly reaching peak firing rate and displaying an exponential decay in returning to the pre-burst rate. During bursts, spike durations increased, and spike amplitudes decreased, while riding on an arc of depolarization around peak rate. In comparison to those from lactating rats in vitro, the rising phase of male bursts was more rapid, the decay phase was slower, and the rising phase of the spike after hyperpolarization was faster. No significant differences, however, were seen in burst characteristics that are most important in determining the amount of peptide release: burst amplitudes (the number of spikes in a burst), firing frequency within bursts or peak firing rate. Thus, we conclude that OT neurons in males are capable of burst firing highly similar to that seen in lactating rats.

Action Potentials↗
PubMed2005

Effect of chronic ethanol ingestion on Purkinje and Golgi cell firing in vivo and on motor coordination in mice.

As motor coordination impairment is a common symptom of acute and chronic alcohol intoxication, different studies have been conducted on cerebellar Purkinje cell sensitivity to ethanol since Purkinje cell firing constitutes the final integrative output of the cerebellar cortex. However, the effects of chronic ethanol ingestion on Purkinje firing and other cerebellar neurons such as Golgi cells remain unknown. Here, we studied the extracellular discharge of Purkinje and Golgi cells in four groups of non-anesthetized mice drinking ad libitum either 0%, 6%, 12% or 18% ethanol isocallorically compensated with sucrose 25% during a 3-month period. No difference in Golgi cell firing was found with respect to ethanol consumption. The only group that presented significant differences in Purkinje cell firing compared to the other groups was the 18% ethanol-drinking group. These mice presented decreased simple spike and complex spike firing and increased complex spike duration and pause. The 18% ethanol-drinking group was also the only one to present a slight but significant motor coordination impairment (evaluated by rotarod and runway) in naïve task. No motor coordination impairment was noticed in task learned before ethanol consumption. These results suggest that chronic high doses of ethanol are necessary to produce Purkinje cell firing alterations and measurable motor coordination impairment in naïve task. These alterations in Purkinje cell firing did not affect the ability to learn or to recall a motor coordination task.

Action Potentials↗
PubMed2006

Firing pattern of rat hippocampal neurons: a perforated patch clamp study.

To test whether the slow afterhyperpolarization (sAHP) underlies the filter function of hippocampal granule cells (GCs), we compared the sAHP and spike frequency adaptation between granule cells and CA3 pyramidal cells (PCs) in hippocampal slices employing gramicidin perforated patch clamp recordings to best preserve the physiological cytoplasmic constitution. sAHPs were evoked in GCs and PCs with trains of action potentials in current clamp mode and showed comparable kinetics in both types of cells. The threshold frequency (500 ms firing) triggering a detectable sAHP was approximately 10 Hz and approximately 3 Hz in GCs and PCs, respectively. Half maximal sAHPs were reached at 30 Hz and 8 Hz in GCs and PCs, respectively. Maximal amplitude of sAHPs in GCs amounted to approximately 3.5 mV, was approximately 2-fold smaller than in PCs and could not be further increased with higher firing frequencies. The time course of sAHP activation was investigated with 50 Hz trains of action potentials applied for increasing durations. In both types of cells, the sAHP amplitude increased with a time constant of approximately 400 ms. Nevertheless, sAHP never exceeded 4 mV in GCs but rose to approximately 12 mV in PCs when cells fired for 3 s. The repetitive firing pattern of GCs and PCs was compared by injecting current amplitudes adjusted to provoke an initial firing frequency of 50 Hz. In GCs firing frequency declined slower (tau = 229 ms) and leveled off at a higher tonic firing frequency (28 Hz) when compared to PCs (tau = 126 ms, 18 Hz). We conclude that the intrinsic excitability of GCs cannot be primarily regulated by the sAHP. The sAHP in GCs is minimal most likely due to a small sAHP-channel density as well as to a more rigid control of intracellular Ca(2+) levels.

Animals↗
PubMed2006

Does the frequency content of the surface mechanomyographic signal reflect motor unit firing rates? A brief review.

The purpose of this review is to examine the literature that has investigated the potential relationship between mechanomyographic (MMG) frequency and motor unit firing rates. Several different experimental designs/methodologies have been used to address this issue, including: repetitive electrical stimulation, voluntary muscle actions in muscles with different fiber type compositions, fatiguing and non-fatiguing isometric or dynamic muscle actions, and voluntary muscle actions in young versus elderly subjects and healthy individuals versus subjects with a neuromuscular disease(s). Generally speaking, the results from these investigations have suggested that MMG frequency is related to the rate of motor unit activation and the contractile properties (contraction and relaxation times) of the muscle fibers. Other studies, however, have reported that MMG mean power frequency (MPF) does not always follow the expected pattern of firing rate modulation (e.g. motor unit firing rates generally increase with torque during isometric muscle actions, but MMG MPF may remain stable or even decrease). In addition, there are several factors that may affect the frequency content of the MMG signal during a voluntary muscle action (i.e. muscle stiffness, intramuscular fluid pressure, etc.), independent of changes in motor unit firing rates. Despite the potential influences of these factors, most of the evidence has suggested that the frequency domain of the MMG signal contains some information regarding motor unit firing rates. It is likely, however, that this information is qualitative, rather than quantitative in nature, and reflects the global motor unit firing rate, rather than the firing rates of a particular group of motor units.

Action Potentials↗
PubMed2003

Modulation of action potential firing by iberiotoxin and NS1619 in rat dorsal root ganglion neurons.

The present study investigated the effects of iberiotoxin (IbTx), a peptide toxin blocker of large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels and NS1619, a BK(Ca) channel opener, on action potential firing of small and medium size afferent neurons from L6 and S1 dorsal root ganglia of adult rats. Application of IbTx (100 nM) reduced whole-cell outward currents in 67% of small and medium size neurons. Analysis of action potential profile revealed that IbTx significantly prolonged the duration of action potential and increased firing frequency of afferent neurons. IbTx did not significantly alter the resting membrane potential, threshold for action potential activation and action potential amplitude. The benzimidazolone NS1619 (10 microM) increased opening activity of a Ca(2+)-dependent channel as assessed by single channel measurements. In contrast to IbTx, NS1619 reversibly suppressed action potential firing, attributable to increases in threshold for evoking action potential, reduction in action potential amplitude and increases in amplitude of afterhyperpolarization. The effect of NS1619 on neuronal firing was sensitive to IbTx, indicating the attenuation of neuronal firing by NS1619 was mediated by opening BK(Ca) channels. NS1619 also reduced neuronal hyperexcitability evoked by 4-aminopyridine (4-AP), a transient-inactivated K(+) channel (A-current) blocker, in an IbTx-sensitive manner. These results indicate that IbTx-sensitive BK(Ca) channels exist in both small and medium diameter dorsal root ganglion (DRG) neurons and play important roles in the repolarization of action potential and firing frequency. NS1619 modulates action potential firing and suppresses 4-AP-evoked hyperexcitability in DRG neurons, in part, by opening BK(Ca) channels. These results suggest that opening BK(Ca) channels might be sufficient to suppress hyperexcitability of afferent neurons as those evoked by stimulants or by disease states.

Action Potentials↗
PubMed2006

Subthalamic nucleus neurones in slices from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mice show irregular, dopamine-reversible firing pattern changes, but without synchronous activity.

The loss of dopamine in idiopathic or animal models of Parkinson's disease induces synchronized low-frequency oscillatory burst-firing in subthalamic nucleus neurones. We sought to establish whether these firing patterns observed in vivo were preserved in slices taken from dopamine-depleted animals, thus establishing a role for the isolated subthalamic-globus pallidus complex in generating the pathological activity. Mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) showed significant reductions of over 90% in levels of dopamine as measured in striatum by high pressure liquid chromatography. Likewise, significant reductions in tyrosine hydroxylase immunostaining within the striatum (>90%) and tyrosine hydroxylase positive cell numbers (65%) in substantia nigra were observed. Compared with slices from intact mice, neurones in slices from MPTP-lesioned mice fired significantly more slowly (mean rate of 4.2 Hz, cf. 7.2 Hz in control) and more irregularly (mean coefficient of variation of inter-spike interval of 94.4%, cf. 37.9% in control). Application of ionotropic glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 2-amino-5-phosphonopentanoic acid (AP5) and the GABA(A) receptor antagonist picrotoxin caused no change in firing pattern. Bath application of dopamine significantly increased cell firing rate and regularized the pattern of activity in cells from slices from both MPTP-treated and control animals. Although the absolute change was more modest in control slices, the maximum dopamine effect in the two groups was comparable. Indeed, when taking into account the basal firing rate, no differences in the sensitivity to dopamine were observed between these two cohorts. Furthermore, pairs of subthalamic nucleus cells showed no correlated activity in slices from either control (21 pairs) or MPTP-treated animals (20 pairs). These results indicate that the isolated but interconnected subthalamic-globus pallidus network is not itself sufficient to generate the aberrant firing patterns in dopamine-depleted animals. More likely, inputs from other regions, such as the cortex, are needed to generate pathological oscillatory activity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2005

Fire as a global 'herbivore': the ecology and evolution of flammable ecosystems.

It is difficult to find references to fire in general textbooks on ecology, conservation biology or biogeography, in spite of the fact that large parts of the world burn on a regular basis, and that there is a considerable literature on the ecology of fire and its use for managing ecosystems. Fire has been burning ecosystems for hundreds of millions of years, helping to shape global biome distribution and to maintain the structure and function of fire-prone communities. Fire is also a significant evolutionary force, and is one of the first tools that humans used to re-shape their world. Here, we review the recent literature, drawing parallels between fire and herbivores as alternative consumers of vegetation. We point to the common questions, and some surprisingly different answers, that emerge from viewing fire as a globally significant consumer that is analogous to herbivory.

Journal Article↗
PubMed2001

Functional and pharmacological characterization of the modulatory role of serotonin on the firing activity of locus coeruleus norepinephrine neurons.

Previous studies, using in vivo extracellular unitary recordings in anaesthetized rats, have shown that the selective 5-HT(1A) receptor antagonist WAY 100,635 suppressed the firing rate of locus coeruleus (LC) norepinephrine (NE) neurons and that this effect was abolished by lesioning 5-HT neurons. In the present experiments, the selective 5-HT(2A) receptor antagonist MDL 100,907, while having no effect on the spontaneous firing activity of LC neurons in controls, was able to restore NE neuronal discharges following the injection of WAY 100,635. The 5-HT(1A) receptor agonist 8-OH-DPAT enhanced the firing activity of NE neurons and this action was entirely dependent on intact 5-HT neurons, unlike the inhibitory effect of the 5-HT(2) receptor agonist DOI. Taken together, these data indicate that 5-HT(2A) but not 5-HT(1A) receptors controlling LC firing activity are postsynaptic to 5-HT neurons. Prolonged, but not subacute, administration of selective 5-HT reuptake inhibitors (SSRIs) produces a decrease in the spontaneous firing activity of LC NE neurons. MDL 100,907 partially reversed this suppressed firing activity of LC neurons in paroxetine-treated rats. Although the alpha(2)-adrenoceptor antagonist idazoxan also enhanced the firing activity of NE neurons in paroxetine-treated rats, this increase was similar to that obtained in controls. In conclusion, prolonged SSRI treatment enhances a tonic inhibitory influence by 5-HT on LC neurons through postsynaptic 5-HT(2A) receptors that are not located on NE neurons. A speculative neuronal circuitry accounting for these phenomena on LC NE activity is proposed.

5,7-Dihydroxytryptamine↗
PubMed1999

Involvement of peripheral NMDA and non-NMDA receptors in development of persistent firing of spinal wide-dynamic-range neurons induced by subcutaneous bee venom injection in the cat.

To study the roles of peripheral excitatory amino acids receptor subtypes N-methyl-D-aspartate (NMDA) and non-NMDA receptors in persistent nociception, extracellular single unit recording technique was used to assess the effects of a single dose NMDA and non-NMDA receptor antagonists, AP(5) (5-aminophosphonovaleric acid) and CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) or DNQX (6,7-dinitroquinoxaline-2,3-dione), on s.c. bee venom-induced increase in firing of wide-dynamic-range (WDR) neurons in the spinal dorsal horn of the urethane-chloralose anesthetized cats. Subcutaneous bee venom injection into the cutaneous receptive field resulted in a single phase of increased firing of WDR neurons over the background activity for more than 1 h. Local pre-administration of AP(5) (200 microg/100 microl) or CNQX (8.3 microg/100 microl) into the bee venom injection site produced 94% (1.01+/-0.96 spikes/s, n=5) or 76% (2.97+/-0.58 spikes/s, n=4) suppression of the increased neuronal firing when compared with local saline (16.32+/-4.55 spikes/s, n=10) or dimethyl sulfoxide (DMSO) (12.37+/-6.36 spikes/s, n=4) pre-treated group, respectively. Local post-administration of the same dose of AP(5) produced a similar result to the pre-treatment group with a 67% inhibition of the mean firing rate, however, the same treatment with CNQX and even a higher dose of DNQX (100 microg/100 microl) did not produce any inhibition of the neuronal firing induced by s.c. bee venom injection (DNQX vs. DMSO: 23.91+/-0. 25 vs. 22.14+/-0.04 spikes/s, P=0.0298, n=5). In the control experiments, local pre-administration of the same dose of AP(5) or CNQX into a region on the contralateral hindpaw symmetrical to the bee venom injection site produced no significant influence on the increased firing of the WDR neurons [contralateral AP(5) vs. saline: 14.17+/-6.27 spikes/s (n=5) vs. 16.32+/-4.55 spikes/s (n=10), P0.05; contralateral CNQX vs. DMSO: 12.85+/-6.38 spikes/s (n=4) vs. 12. 37+/-6.36 spikes/s (n=4), P0.05], implicating that the suppressive action of local AP(5) or CNQX was not the result of systemic effects. The present results suggest that activation of the peripheral NMDA receptors is involved in both induction and maintenance, while activation of non-NMDA receptors is only involved in induction, but not in the maintenance of persistent firing of the dorsal horn WDR neurons induced by s.c. bee venom injection.

2-Amino-5-phosphonovalerate↗