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Correlated firing of retinal ganglion cells.

Even in the absence of visual stimulation, retinal ganglion cells have a substantial maintained discharge. This maintained discharge is not generated independently within each ganglion cell, because the unstimulated activity of two neighboring ganglion cells can be remarkably correlated. These correlations show that two such cells respond together to strong, spontaneous signals from more distal retinal neurons and that, in some cases, ganglion cells even have effects on each other. Observations of correlated firing can give insights not only into the sources of maintained activity but also into retinal connections and signal processing. Correlating firing at the retinal level also has important implications for the use of correlation analysis to study connections between cells in higher visual centers. Much recent attention has focused on the role that correlated firing may play in forming appropriate, ordered connections to a target structure.

Action Potentials↗

Transcorneal electrical stimulation rescues axotomized retinal ganglion cells by activating endogenous retinal IGF-1 system.

PURPOSE: To investigate the effect of transcorneal electrical stimulation (TES) on the survival of axotomized RGCs and the mechanism underlying the TES-induced neuroprotection in vivo. METHODS: Adult male Wistar rats received TES after optic nerve (ON) transection. Seven days after the ON transection, the density of the surviving RGCs was determined, to evaluate the neuroprotective effect of TES. The levels of the mRNA and protein of insulin-like growth factor (IGF)-1 in the retina after TES were determined by RT-PCR and Northern and Western blot analyses. The localization of IGF-1 protein in the retina was examined by immunohistochemistry. RESULTS: TES after ON transection increased the survival of axotomized RGCs in vivo, and the degree of rescue depended on the strength of the electric charge. RT-PCR and Northern and Western blot analyses revealed a gradual upregulation of intrinsic IGF-1 in the retina after TES. Immunohistochemical analysis showed that IGF-1 immunoreactivity was localized initially in the endfeet of Muller cells and then diffused into the inner retina. CONCLUSIONS: TES can rescue the axotomized RGCs by increasing the level of IGF-1 production by Muller cells. These findings provide a new therapeutic approach to prevent or delay the degeneration of retinal neurons without the administration of exogenous neurotrophic factors.

Animals↗

Elimination of neurokinin-1 receptor neurons in caudal nucleus reverses the effects of systemic bicuculline on c-Fos expression in rat trigeminal sensory nucleus: I. High intensity electrical stimulation of the trigeminal ganglion.

Although neurokinin-1 receptor (NK-1)-bearing neurons are distributed in lamina I of the trigeminal caudal nucleus (Vc) and constitute major projection neurons, little is known about their fundamental role(s) in nociceptive processing. This study examines the effect of intra cisterna magna injection of substance P (SP) conjugated to saporin (SP-Sap; 5 microM, 5 microl) [with/without systemic administration of bicuculline] on c-Fos expression in the trigeminal sensory nucleus (TSN) induced 2 h after 10 min repetitive electrical stimulation of the trigeminal ganglion (TG) at high intensity (1.0 mA, 5 Hz, 5 ms) in the urethane-anesthetized rat. In the SP-Sap-treated rats, the numbers of NK-1-immunopositive neurons in laminae I and III of the Vc decreased compared with rats similarly pretreated with saline (Sal; 5 microl) or blank-saporin (Bl-Sap; 5 microM, 5 microl). In Sal- or Bl-Sap-treated controls, high intensity stimulation induced c-Fos expression in neurons throughout the full extent of ipsilateral superficial layers of the Vc (VcI/II), magnocellular zone of the Vc (VcIII/IV) and the dorsal or dorsomedial subdivisions of the rostral TSN above the obex (trigeminal principal, oral (Vo) and interpolar nuclei). Preadministration of bicuculline (2 mg/kg, i.p.) decreased the numbers of c-Fos-immunopositive neurons in the VcI/II, VcIII/IV and Vo in Sal- or Bl-Sap-treated controls. In contrast, high intensity stimulation induced less c-Fos-immunopositive neurons in the VcI/II and Vo of rats treated with SP-Sap compared with those in Sal- or Bl-Sap-treated controls. In SP-Sap-treated rats preadministered with bicuculline, the numbers of c-Fos-immunopositive neurons in the VcI/II and Vo were increased compared with the SP-Sap-treated rats preadministered with Sal. These results suggest that NK-1-immunopositive neurons in laminae I and III of Vc play a pivotal role in the nociceptive specific processing in the TSN through GABA(A) receptors.

Animals↗

Electrical stimulation increases phosphorylation of tyrosine hydroxylase in superior cervical ganglion of rat.

Electrical stimulation of the superior cervical ganglion of the rat increased the phosphorylation of tyrosine hydroxylase (tyrosine 3-monooxygenase, EC 1.14.16.2) in this tissue. Ganglia were incubated with [32P]Pi for 90 min and were then electrically stimulated via the preganglionic nerve. Tyrosine hydroxylase was isolated from homogenates of the ganglia by immunoprecipitation followed by polyacrylamide gel electrophoresis. 32P-labeled tyrosine hydroxylase was visualized by radioautography, and the incorporation of 32P into the enzyme was quantitated by densitometry of the radioautograms. Stimulation of ganglia at 20 Hz for 5 min increased the incorporation of 32P into tyrosine hydroxylase to a level 5-fold that found in unstimulated control ganglia. The increase in phosphorylation of tyrosine hydroxylase was dependent on the duration and frequency of stimulation. Preganglionic stimulation did not increase the phosphorylation of tyrosine hydroxylase in a medium that contained low Ca2+ and high Mg2+. Increases in phosphorylation were reversible; within 30 min after the cessation of stimulation, the incorporation of 32P into tyrosine hydroxylase decreased to the level found in unstimulated ganglia. The nicotinic antagonist hexamethonium reduced the increase in 32P incorporation into tyrosine hydroxylase by about 50%, while the muscarinic antagonist atropine had no effect. Thus, preganglionic stimulation appeared to increase the phosphorylation of tyrosine hydroxylase in part by a nicotinic mechanism and in part by a noncholinergic mechanism. Antidromic stimulation of ganglia also increased the phosphorylation of tyrosine hydroxylase. Two-dimensional gel electrophoresis revealed that electrical stimulation also increased the incorporation of 32P into at least six other phosphoproteins in the ganglion.

Animals↗

Some properties of the transmitter release mechanism at the rat ganglionic synapse during potassium stimulation.

In the present investigation a study has been made using intracellular recordings in the rat superior cervical ganglion of the mode of transmitter release induced by raised external potassium ion concentration (40 mM), after acetylcholine synthesis has been blocked by hemicholinium-3. It is shown that the progressive decline in the rate of acetylcholine output from the ganglion is related to a decrease in the number of quanta being released. Furthermore, under these conditions there is no evidence for a reduction in the size of the transmitter quantum. The statistical foundations of the quantal release process at the rat ganglionic synapse have been investigated by comparing the distribution of the number of miniature EPSPs during successive constant time intervals in the tracings with the corresponding Poisson and binomial predictions. Analyses have shown that the probability for a quantum to be released is so small as to produce a binomial distribution of responses indistinquishable fro- the corresponding Poisson distribution, both at the beginning of the potassium-induced quantum discharge and when transmitter release level is low after exhaustion of acetylcholine tissue content.

Acetylcholine↗

Exogenous growth factors stimulate the regeneration of ganglion cells in the chicken retina.

Recent reports have found that the posthatch chicken retina has the capacity for neuronal regeneration. The purpose of this study was to test whether the types of cells destroyed by neurotoxic lesions influence the types of cells that are regenerated, and whether exogenous growth factors stimulate neural regeneration in the chicken retina. N-methyl-D-aspartate (NMDA) was used to destroy amacrine and bipolar cells; kainate was used to destroy bipolar, amacrine, and ganglion cells; colchicine was used to selectively destroy ganglion cells. Following toxin-induced damage, bromo-deoxyuridine was used to label proliferating cells. In some animals, growth factors were injected into the vitreous chamber of the eye. We found that the proliferation of cells within the retina was stimulated by toxin-induced cell loss, and by insulin and FGF2. After either kainate- or colchicine-induced retinal damage, some of the newly generated cells expressed markers and had the morphology of ganglion cells. The combination of insulin and FGF2 stimulated the regeneration of ganglion cells in kainate- and colchicine-treated retinas. We conclude that exogenous growth factors can be used to stimulate neural regeneration in the retina. We propose that the type of neuron destroyed in the retina may allow or promote the regeneration of that neuronal type.

Animals↗

Possible involvement of nitric oxide in carbachol-induced activation of transglutaminase in rat superior cervical sympathetic ganglia.

The addition of a muscarinic agonist, carbachol (Carb, 0.1 mM), to a physiological medium markedly increased Ca(2+)-dependent transglutaminase (TG) activity (approximately 10-fold) in isolated rat superior cervical sympathetic ganglia (SCG) following in vitro aerobic incubation for 30 min at 37 degrees C. The Carb-evoked stimulation of ganglionic TG activity was considerably reduced (-51%) in the presence of NG-monomethyl-L-arginine (L-NMMA, 50 microM), a selective inhibitor of nitric oxide (NO) synthase. While the suppressant effect of L-NMMA was completely eliminated by the addition of an excess concentration of L-arginine (0.5 mM), a precursor of NO. These observations imply that Carb-induced TG activation possibly involves NO mediation in SCG tissue. The Carb-induced elevation in ganglionic TG activity was markedly reduced (-84%) at as early as 15 min of incubation in the medium containing hemoglobin (Hb) (20 microM), an agent that scavenges only extracellular NO gas. Thus, it is evident that a large fraction of NO released from inside the neuronal cells to extracellular space could rapidly diffuse back into the same group of cells to induce activation of the tissue TG. Methylene blue (MB), an inhibitor of soluble guanylate cyclase (GC), at 0.5 mM, a concentration which is effective in almost abolishing the Carb-evoked synthesis of cyclic GMP (cGMP), had no effect on ganglionic TG activation induced by Carb. Therefore, an increase in cGMP synthesis mediated by NO might not participate in NO-dependent ganglionic TG activation following the stimulation with Carb.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Anti-inflammatory effects of tianrong acupoint on blood vessels of dura mater.

Although Tianrong acupoint (SI 17) is used for migraine headache, its mechanism of action remains obscure. The effects of Tianrong acupoint therapy on neurogenically-mediated plasma protein extravasation (125I-BSA) in rat dura mater induced by electrical stimulation of the right trigeminal ganglion was studied. When the unilateral trigeminal ganglion was stimulated (5 Hz, 1.2 mA, 5 msec for 5 min), the ratio of stimulated side/unstimulated side (cpm/mg) was 1.6663 +/- 0.0217. The plasma extravasation was blocked by different kinds of treatment in different degrees. The order of the ratio was as follow: Tianrong acupoint therapy (1.0917 +/- 0.0266) and Tianrong electrical needle therapy (1.1281 +/- 0.0227) < Tianrong acupoint injection with normal saline (1.325 +/- 0.0444) < Quchi acupoint (LI 11) injection with prednisolonum (1.5284 +/- 1.1624). The results indicated that Tianrong acupoint therapy could inhibit the neurongenic inflammation on the affected side.

Acupuncture Points↗

THE EFFECTS OF CHOLINE AND OTHER FACTORS ON THE RELEASE OF ACETYLCHOLINE FROM THE STIMULATED PERFUSED SUPERIOR CERVICAL GANGLION OF THE CAT.

When the superior cervical ganglion of the cat was perfused with Locke solution, the amount of acetylcholine released into the perfusate decreased during successive periods of repetitive stimulation of the preganglionic nerve. Addition of choline to the perfusion fluid prevented this decrease. Choline also significantly increased (P<0.01) the initial output of acetylcholine. In contrast, variation of the physostigmine concentration or of the pCO(2) and pH of the perfusion fluid had no statistically significant effect (P>0.05) upon the initial release of acetylcholine.

Acetylcholine↗

Experimental evidence for beta adrenergic blocking properties of propafenone and for their potential clinical relevance.

The magnitude and biological relevance in vivo of the beta-blocking properties, observed in vitro, of propafenone remains controversial. We studied the effects of propafenone on the heart rate response to graded stimulation of the right stellate ganglion in 13 anaesthetized, vagotomized cats. The decentralized ganglion was stimulated (3 ms, 10 to 15 V) for periods of 45 s at frequencies from 1 to 14 Hz. The effects of sympathetic stimulation on heart rate were evaluated by the relationship between stimulation frequency and changes in heart rate from control. The relationship was significantly displaced downward and to the right by propafenone (4 mg.kg-1, n = 7), indicating a blunted response to sympathetic stimulation. This effect was lost at the highest frequencies. The frequency range at which propafenone was effective is the same as that elicited in cardiac sympathetic nerves by acute myocardial ischaemia. With propranolol (0.5 mg.kg-1 n = 4), the effects on the heart rate response were similar but of greater magnitude. Another sodium channel blocker (flecainide, 4 mg.kg-1 n = 2) was administered, and no changes were observed in the heart rate response. Thus, propafenone has significant beta-blocking effects, which would be of clinical relevance during the reflex sympathetic activation consequent to myocardial ischaemia.

Adrenergic beta-Antagonists↗

Intracellular recordings from the stellate ganglion of the cat.

1. Intracellular recordings were made, in vitro, and in situ, from neurones of the cat stellate ganglion. 2. Preganglionic stimulation, in vitro, via the T3 ramus or post-ganglionic stimulation via the ventral ansa, dorsal ansa or stellate cardiac nerve evoked graded synaptic responses which led to the discharge of one or more action potentials. Since the conduction velocities of fibres converging onto a single cell may vary, their convergence may mean that there is an interaction in the stellate ganglion between functionally different pathways. 3. Most neurones in the stellate ganglion receive synaptic input from fibres of both central and peripheral origin. 4. Intracellular recordings were made, in situ, from neurones of the cat stellate ganglion attached via the stellate cardiac nerve to the rest of the animal. When peripheral sympathetic afferent input to the stellate ganglion was increased by occluding the descending aorta, some of the neurones exhibited an increase in excitatory post-synaptic potentials (e.p.s.p.s) and/or action potentials. Most of the synaptic input recorded from the ganglion cells in situ had a close relationship with the cardiac cycle and/or respiration. 5. These data and our previous studies support the contention that sympathetic efferent nerve activity can be modified by peripheral excitatory inputs and that these neural connexions may function as pathways for a peripheral reflex at the level of the paravertebral ganglion.

Action Potentials↗

Stimulation of left stellate ganglion prolongs Q-T interval in patients with palmar hyperhidrosis.

With the advent of transthoracic video-assisted endoscopic electrocautery of the second and the third sympathetic ganglia for the treatment of palmar hyperhidrosis, it is possible to approach the stellate ganglia with ease. To see whether stimulation of stellate ganglia in humans is similar to the case in dogs, we stimulated the sympathetic ganglia in 18 palmar hyperhidrosis patients with a coagulation power of 5 W at a frequency of three times every 2 s. We found that left stellate stimulation prolongs the Q-T interval and increases the heart rate, whereas right stellate stimulation affects the Q-T interval and heart rate insignificantly, just like the case in dogs in which the left stellate ganglion predominates the right one in determining the Q-T interval. Left stellate stimulation after destruction of the left second and third ganglia also prolongs the Q-T interval, suggesting that the left stellate ganglion is more important in determining the Q-T interval.

Adolescent↗

Increased spiral ganglion cell survival in electrically stimulated, deafened guinea pig cochleae.

For implanted electronic prostheses to function successfully in the deaf, residual spiral ganglion neurons are presumed to be necessary. Several studies have tried to determine the effects cochlear electrode implantation and electrical stimulation have on the neurons of the spiral ganglion. Little work has been published, however, on the trophic effects of electrical stimulation on cell survival after cochlear damage by ototoxicity. This report presents the results of an investigation to determine the effects of early intracochlear electrical stimulation on spiral ganglion neuron survival after chemically induced deafness in young guinea pigs. A significantly larger number of spiral ganglion cells remained in stimulated ears 6 weeks after deafening than were seen in the unstimulated ears of the same animals. These results suggest that early implantation after acquired deafness may affect the success obtainable with electronic hearing prostheses.

Animals↗