Characteristics of the neuronal reaction of the substantia nigra to nociceptive stimulation

The nature of neurone response of substance nigra (SN) to nociceptive stimulation of the cat's peroneal nerve has been studied. The recording of neurone SN firing rate revealed that the majority (71.0%) of the SN neurones responded to the nociceptive repetitive stimulation of the peroneal nerve. But the thresholds of nociceptive activation in SN neurones turned to be very high. As a result of it the number of SN neurones responding to repetitive peroneal stimulation was twice as many as the number of cells responding to single stimulation of the nerve. The intravenous injection of naloxone in dose 1.0 mg/kg changed both excitatory and inhibitory responses in majority (71.4%) of SN neurones responding to repetitive peroneal stimulation. Naloxone did not modify the firing rate of neurones nonresponsive to nociception.     

Activity pattern of suboesophageal ganglion cells innervating the salivary glands of the locust Locusta migratoria

The salivary gland of the locust, Locusta migratoria, is innervated from the suboesophageal ganglion by two neurones, SN1 and SN2 which innervate the gland via the salivary gland nerve (nerve 7B of the suboesophageal ganglion). In addition, like most other peripheral nerves of the head, this nerve carries on its outer surface axons and neurohaemal terminal ramifications of the so called satellite nervous system, established by a group of neurosecretory cells also located in the suboesophageal ganglion. These superficial collaterals ramify over the nerve from its origin in the head to its terminals within the gland in the thoracic segments.Nerve 7B was recorded chronically in freely moving locusts. Both salivary neurones are active during and shortly before feeding, as defined by continuous rhythmic activity of the mandibular closer muscle (M9). The activity of the salivary neurones, particularly that of SN2, thus resembles that of the satellite neurones as described recently. While SN2 ceases firing at the end of a feeding bout, SN1 continues firing for a short period. Also, SN1 fires short bursts of impulses for a few minutes following the end of a feeding bout. Similar bursts also occur at random intervals during the long-lasting phases between feeding events.Abbreviations SN1 salivary neurone 1 - SN2 salivary neurone 2 - M9 mandibular closer muscle - DUM dorsal unpaired median - LMN labral median nerve     

NO donors transform neuronal response to glutamate

Electrophysiological experiments on three identified neurones were performed. Two NO donors, sodium nitroprusside (SNP) and sodium nitrite, as well as NO synthase inhibitor, were used. In each neurone, bath application of glutamate caused hyperpolarization and suppression of firing. Combined application of glutamate and SNP resulted in that the same cells responded to identical glutamate solutions with depolarization and excitation. Application of N-monomethyl-L-arginin (NMMA) arrested the glutamate-induced firing and depolarization. The findings suggest involvement of NO in the mechanism of transformation of glutamate-induced inhibition into excitation and a mediation of the latter by the N-methyl-D-aspartate-like receptors in the Helix brain.     

Differential effects of prostaglandin F2 alpha on oxytocinergic and non-oxytocinergic neurones in the paraventricular nucleus of the lactating rat

The effects of the prostaglandin F2 alpha (PGF2 alpha) given into the third cerebral ventricle on the unit activity of neurosecretory neurones in the paraventricular nucleus (PVN) were studied in urethane-anesthetized rats. The firing activity of PVN neurones was recorded extracellularly and 50 neurones were antidromically identified as neurosecretory neurones. Thirty of them were classified oxytocinergic neurones because they gave a burst of action potential 12-15 sec before reflex milk ejection and the remaining twenty PVN neurones which showed no response prior to reflex milk ejections were regarded as non-oxytocinergic ones. Twenty-five (83%) of the30 oxytocinergic neurones increased in the firing rate following the intraventricular (IVT) injection of PGF2 alpha (500ng in 1 microliter of isotonic saline) and the responses lasted for about 20-30 min. The remaining 5 (17%) oxytocinergic neurones showed no response in the firing rate to IVT PGF2 alpha. Fifteen (75%) of the 20 nonoxytocinergic neurones decreased in the firing activity in response to IVT PGF2 alpha, and the remaining 5 (25%) of them showed no response. IVT injection of isotonic saline (1 microliter) did not affect the firing activity of both the oxytocinergic and nonoxytocinergic cells. The intramammary pressure was slightly increased by the IVT administration of PGF2 alpha. These findings indicate that IVT PGF2 alpha has a differential action on oxytocinergic and non-oxytocinergic neurones in rats.     

Effect of thyroliberin on membrane potential and pattern of spontaneous activity of neurons of the respiratory center in rats in vitro

On frontal brainstem slices of rat by means of whole-clamp recordings, we investigated effects of TRH (10(-8) [symbol: see text]) on membrane potential and firing pattern of the neurones in ventrolateral area of the solitary tract nucleus and pre-Botzinger complex. TRH induced a membrane depolarisation and an increase in spontaneous activity of the respiratory centre neurones. After TRH administration, a shortening of time intervals between the beginning of bursts was found in bursting neurones of the pre-Botzinger complex. In some silent neurones, TRH elicited appearance of firing activity, so the silent neurones of the solitary tract nucleus were transformed into tonic while the silent pre-Botzinger complex neurones were transformed into bursting ones. Thus, there is a direct regulatory effect of TRH on the respiratory centre neurones at the level of their membrane.     

Tryptamine and 5-hydroxytryptamine: actions and interactions of cortical neurones in the rat

The actions of iontophoretically applied tryptamine (T) and 5-hydroxytryptamine (5-HT) were compared on single neurones in the rat somatosensory cortex. The firing rate of the vast majority of neurones tested was depressed by T. However, 5-HT excited and depressed approximately equal numbers of neurones. Depressant effects of 5-HT could be profoundly enhanced by a very weak concurrent application of T (0–10 nA) which itself did not alter the baseline cell firing rate. Excitatory responses to 5-HT were consistently reversed into depressant responses during weak applications of T. These observations could support a modulatory role for endogenous T in 5-HT-mediated transmission in the central nervous system (CNS).     

Presynaptic inhibition of excitatory input from the substantia nigra to caudate nucleus neurons by a substituted quinolinone derivative, 7-[3-(4-(2,3-dimethylphenyl)piperazinyl)propoxy]-2(1H)-quinolinone (OPC-4392)

The effects of a newly synthesized quinolinone derivative, 7-[3-(4-(2,3-dimethylphenyl)piperazinyl) propoxy]-2(1H)-quinolinone (OPC-4392) on neuronal activities of the caudate nucleus (CN) were investigated in cats anesthetized with alpha-chloralose using a microiontophoretic method. In the CN neurons of which spikes elicited by stimulation of the pars compacta of substantia nigra (SN) were suppressed by iontophoretically applied domperidone, a dopamine D-2 receptor antagonist, application of OPC-4392 (100-200 nA) inhibited the spike generation induced by SN stimulation. Conversely, the CN neurons insensitive to domperidone were unaffected by OPC-4392. Iontophoretic application of CPC-4392 up to 200 nA did not affect glutamate-induced firing of the CN neurons, of which the firing was blocked by dopamine less than 100 nA. In addition, OPC-4392 did not inhibit firing induced by bromocriptine, a dopamine D-2 agonist; while domperidone suppressed the bromocriptine-induced firing without affecting the glutamate-induced firing. These results suggest that OPC-4392 acts on the dopaminergic nerve terminals and inhibits excitatory transmission from the SN to the CN.     

Acute actions of marine toxin latrunculin A on the electrophysiological properties of cultured dorsal root ganglion neurones

The effects of latrunculin A, isolated from the nudibranch Chromodoris sp., on the excitability of neonatal rat cultured dorsal root ganglion neurones were investigated using patch-clamp recording and Ca(2+) imaging techniques. Under current-clamp conditions, acute application of latrunculin A (100 microM) reversibly induced multiple action potential firing and significantly increased action potential duration. No significant effects on action potential peak amplitude, threshold of action potential firing, resting membrane potential and input resistance were observed. Under voltage-clamp conditions, significant and dose-dependent suppression of K(+) current was seen with 10-100 microM latrunculin A. Additionally, a significant difference between inhibition of the current measured at the peak and the end of a 100 ms voltage step was seen with 100 microM latrunculin A. Fura-2 fluorescence Ca(2+) imaging revealed that latrunculin A (100 microM) significantly inhibited Ca(2+) transients evoked by KCl-induced depolarisation in all neurones. In 36% of DRG neurones, latrunculin A alone had no effect on intracellular Ca(2+). In 64% of neurones, latrunculin A alone evoked a transient rise in intracellular Ca(2+). Moreover, latrunculin A (10-100 microM) significantly inhibited the mean high voltage-activated Ca(2+) current. The effects of latrunculin A on action potential firing and K(+) currents were attenuated by intracellular phalloidin, an indication that these effects are mediated through actin disruption.     

Interaction of serotonin and nitric oxide (NO) in activation of the serotoninergic system in Helix

Serotonin and the NO donors were shown to induce excitation in all serotoninergic neurones under study and to activate synchronous synaptic input in the Helix brain. The serotonin effects may be blocked by 5,7-DOT and N-monomethyl-L-arginine. The 5,7-DOT blocked activation of the NO-induced synchronous bursts but did not affect their activating effect. The data obtained suggest that serotonin and NO equally regulate the serotoninergic system's function in the snail brain. The effects of serotonin and NO are interconnected and interdependent. A possible role of the NO as a second messenger during serotonin activation and as a serotonin co-transmitter in presynaptic neurones, is discussed.     

侧脑室注射心房钠尿肽对大鼠室旁核单位放电...

We have applied microelectrode technique to record 118 spontaneously firing units from the hypothalamus in rats. Detection of the recording sites showed that 84 were in the paraventricular nucleus (PVN) and 34 were near the PVN (near-PVN). After intracerebroventricular (i.c.v.) administration of atrial natriuretic polypeptide (ANP), 91% (P less than 0.005) of the PVN neurones and 71% (P greater than 0.05) of near-PVN neurones sensitive to ANP showed a significant decrease in spontaneously firing rate. After i.c.v. administration of hypertonic NaCl solution, 64.7% (P less than 0.005) of the PVN neurones and 61.1% (P greater than 0.05) of near-PVN neurones showed a significant increase in firing rate. The results indicate that i.c.v. administration of ANP profoundly inhibits the electrical activity of the PVN neurones, but hypertonic NaCl solution markedly stimulates the PVN neurones.     

Effects of intraoral mechanoreceptor stimulation on reticular formation neurones, in the rabbit

The effects of intraoral mechanoreceptor stimulation on the firing rate of single neurones of the brain stem reticular formation (RF) were investigated in rabbits. 30% of RF neurones responded to periodontal mechanoreceptor stimulation; 16% to mucosal mechanoreceptor stimulation and 6% to both types of stimuli. Periodontal stimulation induced mainly inhibitory effects localized within the mesencephalic and rostral pontine RF. Among periodontal afferents incisors were the most widely represented. The effects of mucosal mechanoreceptor stimulation were predominant in the medullary and pontine RF and they were mainly excitatory. The present results support the hypothesis that brain stem RF neurones can be recruited into regulating mastication and biting also by stimulation of intraoral mechanoreceptors.     

Comparison of spontaneous activity of mesencephalic reticular neurones in the waking state and during pentobarbital anaesthesia.

In rats immobilized by d-Tubocurarine the spontaneous activity of 100 mesencephalic reticular neurones was recorded extracellularly and statistically evaluated before and after repeated intravenous administration of 15 mg/kg doses of Pentobarbital. Number of spontaneously active neurones decreases quasi-linearly with repeated 15 mg/kg Pentobarbital doses. After a 75 mg/kg cumulative dose practically all neurones ceased firing spontaneously, whereas cortical EEG activity fully disappeared after the 90 mg/kg Pentobarbital dose. The firing rate was characterized by the mean interval with its standard deviation. Mean value for the total sample of spontaneously active neurones was 146.7 +/- 192.3 msec without Pentobarbital and increased to 302.7 +/- 367.5 msec after 15 mg/kg and to 400.6 +/- 452.5 msec after 30 mg/kg cumulative dose of Pentobarbital. The 15 mg/kg dose increased the frequency of firing in 5% of neurones only. The most often encountered type of interval histogram in the mesencephalic reticular formation was the exponential type (59% in unanaesthetized state), which was also most sensitive to Pentobarbital. Synchronized activity in bursts, characterized by periodical peaks and dips frequently occurred in neurones with the exponential-like interspike interval density after Pentobarbital administration. On the contrary, neurones with gamma-like and especially with symmetrical-like types of density were less influenced by Pentobarbital. In many neurones a periodical increase in the firing rate (with intervals of tens of seconds) related to the occurrence of spindles was present in the cortical EEG activity.     

V1-Vasopressin Receptors in the Septum of the Rat Brain. Electrophysiological Evidence

Abstract

In slices from the rat brain, extracellular recordings were obtained from single neurones located in the lateral septum, an area known to receive a vasopressinergic innervation. Approximately half of the neurones tested responded to vasopressin by a concentration-dependent increase in firing rate, the lowest effective concentration being in the order of 2 nM. The effect of vasopressin was blocked by a synthetic structural analogue possessing vasopressor and oxytocic antagonistic properties on peripheral vasopressin and oxytocin receptors. Oxytocin had a weak effect in firing septal neurones, whereas a selective oxytocic agonist was totally ineffective. The action of vasopressin on neuronal firing was mimicked by a vasopressor agonist (Phe2-Orn8-VT) but not by a selective antidiuretic agonist (dDAVP). These results indicate that the vasopressin receptors present in rat septum are V1 (vasopressor type) rather than V2 (antidiuretic type) receptors. In addition, we conclude that these receptors, when occupied, lead to increased firing of lateral septal neurones.     

An immunohistochemical and stereological analysis of PSI-induced nigral neuronal degeneration in the rat

Systemic administration of the proteasomal inhibitor I (PSI) to rats was reported to cause progressive nigral dopaminergic neuronal loss but this is disputed. A major controversy centres over the use of manual counting of tyrosine hydroxylase (TH) positive neurons at the level of third cranial nerve as opposed to employing systematic stereological analysis of cell loss in the entire substantia nigra (SN). To provide a method of marking SN neurones independent of protein expression, fluorogold^™ (FG) was stereotaxically injected bilaterally into the striatum of male Wistar rats to retrogradely label nigral dopaminergic neurons. After 1 week, animals were treated with six doses of PSI (8 mg/kg, s.c.) or its vehicle (dimethyl sulphoxide) on alternate days over a 2-week period. Five weeks after the last treatment, PSI-treated animals showed decreased spontaneous locomotor activity and reduced TH positive SN cell number at the level of the third cranial nerve compared to control rats. Manual cell counting showed loss of FG-labelled SN neurones at this level, with a subpopulation of surviving neurons displaying abnormal morphology. Manual counting of all FG-labelled cells in the entire SN also showed regional PSI-induced loss of neurones with both normal and compromised morphology. Stereological optical fractionator estimates of total FG-labelled cell number confirmed the manual cell counting data both at the level of the third cranial nerve and throughout the entire SN. These findings confirm that PSI does cause a persistent nigral dopaminergic neuronal loss. The reason for the lack of reproducibility between laboratories requires further investigation. We suggest that a failure to distinguish between TH-positive neurones with normal and abnormal morphology following PSI administration contributes to equivocal results.     

Postural baroreflex stimuli may affect EEG arousal and sleep in humans

Past research has shown that baroreceptor stimulation can induce sleep. The present study investigated whether the upright posture inhibits sleep by reducing baroreceptor firing. Twenty-eight men were each exposed to four conditions on separate days: 40 degrees head-up tilt with (TP) and without (TN) 45 mmHg positive pressure on the legs and the supine position with (SP) and without (SN) leg pressure. Heart rate and blood pressure changes indicated that baroreceptor firing was strongly reduced by TN and only mildly reduced by TP in 24 subjects. Baroreceptor effects of SP were unclear. SN and SP did not differ significantly in their effects on electroencephalogram (EEG) sleep. Among subjects who showed a normal baroreflex response to tilt, both TN and TP inhibited sleep, but TN caused a persistent elevation of EEG beta activity that did not occur in TP plus a greater delay in sleep onset. TN had no such arousing effects in four subjects who showed little or no baroreflex response to tilt. These results are consistent with the hypothesis that the fall in baroreceptor firing produced by the upright posture contributes to EEG arousal.     

Selective excitation of GABAergic neurons in the substantia nigra of the rat by orexin/hypocretin in vitro

Dysfunction of the orexin/hypocretin neurotransmitter system leads to the sleep disorder narcolepsy. Narcolepsy is characterized by excessive daytime sleepiness and the occurrence of cataplexy--a sudden loss of muscle tone triggered by emotionally arousing events. Both symptoms can be treated with drugs that act on dopaminergic systems. Here we have investigated the effect of orexins on the firing of dopaminergic and GABAergic neurons of the substantia nigra (SN) in brain slices. Surprisingly, dopaminergic neurons in pars compacta were unaffected by orexins. In contrast, bath application of orexin A (100 nM) or orexin B (5-300 nM) greatly increased the firing rate of GABAergic neurons in pars reticulata. The orexin B-mediated excitation was unaffected by blocking synaptic transmission (using low-Ca2+/high-Mg2+ solution). However, the effect of orexin B was reduced significantly by thapsigargin (1 microM) and inhibitors of protein kinase A. The presence of orexinergic fibres in the SN pars reticulata was demonstrated by immunohistochemical methods with the fibre density increasing in the rostrocaudal direction. The orexin excitation of SN reticulata cells may help to maintain their high firing rate during waking. Furthermore, the absence of orexin effects in narcolepsy may predispose affected individuals to attacks of cataplexy.     

Properties of a symmetric pair of serotonin-containing neurones in the cerebral ganglia of Planorbis.

1. There is a bilaterally symmetric pair of large serotonin-containing neurones in the cerebral ganglia of Planorbis corneus. 2. In some animals these neurones are connected by a non-rectifying electrotonic synapse, and fire in synchrony even at prolonged high frequency. In other animals the neurones are not coupled, and fire independently except when driven by common input. Occasionally the coupling is weak. 3. Both coupled and non-coupled serotonin neurones have processes in the major nerve trunks of both buccal ganglia. 4. Synapses are made with many neurones in the buccal ganglia. The serotonin neurones can initiate firing in several motoneurones and thus produce movements of the buccal mass. 5. During spontaneous feeding cycles the input and firing pattern of the serotonin neurones do not bear any obvious relation to the movements of the buccal mass. 6. The data suggest that the serotonin neurones are modulatory cells, altering the level of excitability of buccal ganglion neurones.     

Distribution of NO-induced cGMP-like immunoreactive neurones in the abdominal nervous system of the crayfish,Procambarus clarkii

Nitric oxide (NO) acts as a signalling molecule by activating soluble guanylate cyclase and causing accumulation of the second messenger cyclic guanosine 3',5'-monophosphate (cGMP) in target cells. In order to detect the presence of NO-cGMP signalling pathway in the crayfish abdominal nervous system, accumulation of NO-induced cGMP was investigated by anti-cGMP immunochemistry. Some preparations were incubated in a high-K(+) saline containing an inhibitor of cGMP-degrading phosphodiesterase, 3-isobutyl-1-methyxanthine (IBMX), to activate NO generating neurones, which could release NO in the ganglion, and then immunohistochemistry using an anti-cGMP antibody was performed. The other preparations were incubated in NO donor, sodium nitroprusside (SNP) saline containing IBMX before anti-cGMP immunohistochemistry was performed. The distribution of cGMP-like immunoreactive neurones in high-K(+) treated preparations was similar to that of cGMP-like immunoreactive neurones in NO donor treated preparations. About 70-80 cell bodies and many neuronal branches in the neuropilar area of the ganglion were stained, although no neurones showed immunoreactivity unless preparations were activated by either high-K(+) or the NO donor. Some of them were identical neurones, and they were intersegmental ascending interneurones and motor neurones. Sensory afferents that innervates hind gut showed strong cGMP-like immunoreactivity, although no mechanosensory afferents showed any immunoreactivity. These results strongly suggest the presence of an NO-cGMP signalling pathway that regulates neuronal events in the abdominal nervous system of the crayfish.     

Stromal cell-derived factor-1alpha modulation of the excitability of rat substantia nigra dopaminergic neurones: presynaptic mechanisms

In rat substantia nigra (SN), Chemokine (CXC motif) receptor 4 (CXCR4) for the chemokine stromal cell-derived factor (SDF)-1alpha is expressed on dopaminergic (DA) neurones, but also on non-DA cells, suggesting presynaptic actions. Using whole-cell patch-clamp recordings in DA neurones of rat SN slices at a holding potential of -60 mV, we showed here that SDF-1alpha exerts multiple presynaptic effects. First, SDF-1alpha (10 nm) induced an increase in the frequency of spontaneous and miniature GABA(A) postsynaptic currents by presynaptic mechanisms, consistent with the presence of CXCR4 on GABAergic neurones of the SN, as revealed by immunocytochemistry. Second, SDF-1alpha (0.1-1 nm) induced a glutamatergic inward current resistant to tetrodotoxin (TTX), most probably the result of glutamate release from non-neuronal cells. This inward current was not blocked by the CXCR4 antagonist AMD 3100 (1 microm), consistent with the lack of CXCR4 on astrocytes as shown by immunocytochemistry under basal conditions. Finally, SDF-1alpha (10 nm) induced, via CXCR4, an outward G protein-activated inward rectifier (GIRK) current, which was TTX sensitive and prevented by application of the GABA(B) antagonist CGP55845A, suggesting GABA spillover on to GABA(B) receptors. Our results show that SDF-1alpha induces, via presynaptic mechanisms, alterations in the excitability of DA neurones as confirmed by current-clamp experiments.     

侧脑室注射心房钠尿肽对大鼠室旁核单位放电的影响

本实验利用微电极技术在大鼠下丘脑共记录到118个自发放电单位,其中84个位于室旁核(PVN)内,34个位于 PVN 邻近部位。侧脑室注入心房钠尿肽(ANP)后,受其影响的 PVN神经元和 PVN 邻近部位神经元,分别有91%(P<0.005)和71%(P>0.05)表现为自发放电频率减少;侧脑室注入高渗 NaCl 溶液则分别使64.7%(P<0.005)和61.1%(P>0.05)的神经元自发放电频率增加。结果表明,侧脑室注入 ANP 对 PVN 神经元自发放电活动具有明显的抑制作用。