Locus Coeruleus Conditioning Stimulation Research Articles

Effects of l- threo-DOPS, an l-noradrenaline precursor, on locus coeruleus-originating neurons in spinal trigeminal nucleus

Electrophysiological studies using reserpinized cats were performed to examine the effects of l- threo-3,4-dihydroxyphenylserine( l-threo-DOPS) on the noradrenergic pathway from the locus coeruleus (LC)_to the spinal trigeminal nucleus (STN). The spike generation of STN relay neurons induced by trigeminal nerve stimulation was not affected by LC conditioning stimulation nor iontophoretic application of l- threo-DOPS. After intraventricular administrayion of l- threo-DOPS, the inhibition of the spike generation was seen with LC conditioning stimulation and blocked by iontophoretically applied sotalol, suggesting that l-noradrenaline converted from l- threo-DOPS inhibits transmission of STN relay neurons.

Beta-receptor involvement in locus coeruleus-induced inhibition of spinal trigeminal nucleus neurons: Microiontophoretic and HRP studies

Microiontophoretic and HRP studies were performed on cats anesthetized with α-chloralose to determine whether or not the locus coeruleus (LC)- and noradrenaline (NA)-induced inhibition of relay neurons in the subnucleus oralis of the spinal trigeminal nucleus (STN) is mediated by ß-adrenergic receptors. The inhibition of orthodromic spike generation upon intracranial trigeminal nerve stimulation by LC conditioning stimulation and microiontophoretically applied NA (100–200 nA) was antagonized during microiontophoretic application of sotalol, a ß-adrenergic, but not affected by phentolamine, an α-adrenergic antagonist. When HRP at doses of 300–500 nA was applied for 5–15 min to the immediate vicinity of the STN relay or interneuron, which was electrophysiologically identified by stimulating the ipsilateral trigeminal nerve and contralateral medial lemniscus, the injection site was localized to an area 0.3 mm in diameter and HRP-reactive cells were found in the ipsilateral LC, dorsal raphe nucleus and periaqueductal gray ventral to the aqueduct. These results strongly suggest that NA released from the nerve terminals of LC cells inhibits transmission in the STN relay neuron via ß-adrenergic receptors.

Inhibition from locus coeruleus of nucleus accumbens neurons activated by hippocampal stimulation

Electrophysiological studies using rats were performed to examine the influence of locus coeruleus (LC) on nucleus accumbens (Acc) neurons. Spike generation by hippocampal stimulation was inhibited by both LC conditioning stimulation and iontophoretic application of noradrenaline, but spikes elicited by stimulation of parafascicular nucleus of thalamus were rarely affected by LC conditioning stimulation or noradrenaline. The LC-induced inhibition was antagonized by iontophoretic sotatol, but not by phentolamine, suggesting that noradrenaline derived from the LC inhibits the Acc neurons receiving input from the hippocampus, probably acting on a β-adrenergic receptor.

Effect of noradrenergic drugs on response of posterior hypothalamic neurons to stimulation of the locus coeruleus (LC) and the central nucleus of amygdala (ACE) in rats.

Physiological and pharmacological natures of neuronal responses in posterior hypothalamus (HPA) elicited by stimulation of LC and ACE were investigated in rats. Most extracellularly recorded HPA neurons (186 units) remained unaffected by LC stimulation: 4 showed spike discharges at latencies of 5 to 16 msec, 1 gave rise to an antidromic spike at latencies of 3 to 4 msec, 22 showed inhibition extending from 12 to 40 msec after LC stimulation. When applied iontophoretically, phenylephrine slightly intensified the inhibition by LC stimulation, E-643 partly blocked the inhibition with lower ejection currents and increased it with higher ejection currents, Clonidine intensified the inhibition for the most part, and other three drugs, isoproterenol, dopamine and acetylcholine, hardly produced any effect on inhibition. In 4 of 22 units which snowed inhibition to LC stimulation, conditioning stimulation of LC failed to produce any effect on discharge patterns of HPA neurons elicited by ACE stimulation. Only in 1 unit, however, it produced a significant reduction in latency and spike number. An iontophoretic application of the above-mentioned 6 drugs did not mimic the inhibitory effect of conditioning stimulation of LC on the discharge patterns elicited by ACE stimulation. It is likely that an ascending NA pathway from LC to HPA exerts some inhibitory effect on the input from ACE to HPA, but the pharmacological nature of inhibition remains to be clarified.

Inhibition from locus coeruleus of caudate neurons activated by nigral stimulation

Electrophysiological studies were performed to determine if the locus coeruleus (LC) plays a role in regulating activity of caudate nucleus (CN) neurons. Cats were anesthetized with alpha-chloralose and when conditioning stimuli were applied to the LC, preceding the test stimulus, there was a significant inhibition of spike generation in 33 out of 93 CN neurons transsynaptically activated by test stimulus to the pars compacta of the substantia nigra (SN). An inhibition of spike generation with LC conditioning stimulation and iontophoretic application of noradrenaline was obtained in 9 out of the same 23 CN neurons and 8 neurons remained unaffected with either treatment. In contrast to these neurons, LC conditioning stimulation did not affect the spontaneous firing and spike generation of CN neurons antidromically excited by SN stimulation. Spike firing of CN neurons transsynaptically activated by motor cortex stimulation remained unaffected with LC conditioning stimulation. These results suggest that noradrenaline derived from the LC produced an inhibition of spike generation in about one-third of CN neurons tested and transsynaptically activated by SN stimulation.

EFFECT OF STIMULATION OF LOCUS COERULEUS ON THE EVOKED POTENTIAL IN THE AMYGDALA IN RATS

Effects of stimulation of the locus coeruleus (LC) on evoked potential in the medial amygdala elicited by stimulation of the olfactory bulb (OB-AME potential) were studied in gallamine-immobilized rats. The amplitude of the OB-AME potential was inhibited 27.5% by the conditioning stimulation of LC delivered 30 msec before the test stimulation. The inhibitory effect of LC was reduced by propranolol 5 mg/kg i.p., but not by phentolamine 10 mg/kg i.p.. This effect was also reduced by tetrabenazine 10 mg/kg i.p.. Methamphetamine 5 mg/kg i.p. produced considerable potentiation of the LC inhibitory effect and a reduction of the OB-AME potential itself. These results suggest that the LC plays an inhibitory role in the electrical activity of the medial amygdala.

Feedback loop between locus coeruleus and spinal trigeminal nucleus neurons responding to tooth pulp stimulation in the rat

IGARASHI, S., M. SASA AND S. TAKAORI. Feedback loop between locus coeruleus and spinal trigeminal nucleus neurons responding to tooth pulp stimulation in the rat. BRAIN RES. BULL. 4(1) 75–83, 1979.—Studies were performed to elucidate reciprocal relationships between locus coeruleus (LC) and spinal trigeminal nucleus (STN) neurons responding to tooth pulp (TP) stimulation using rats anesthetized with α-chloralose. LC conditioning stimulation inhibited STN field potential as well as orthodromic spike generation of STN neurons produced by ipsilateral TP stimulation, confirming the previous findings in cats that LC neurons played an inhibitory role in the orthodromic transmission in STN neurons. Forty-one out of 56 LC neurons were activated by ipsilateral TP stimulation and 12 neurons by stimulation of both ipsi- and contralateral TP. STN stimulation usually excited LC neurons with a significantly shorter latency than did TP stimulation, including three LC neurons with a latency of less than 2.0 msec. These results indicate the existence of input from TP to LC neurons via multisynapses. In addition, neurons antidromically activated by STN stimulation were found in LC. It is highly probable, therefore, that there is a feedback loop between LC and STN, which might control input from TP to STN.

Morphine interference with noradrenaline-mediated inhibition from the locus coeruleus

The effect of morphine on inhibition of relay neurons in the spinal trigeminal nucleus (STN) produced by conditioning stimulation of the locus coeruleus (LC) was studied in cats. Alterations in orthodromic and antidromic spike generations in STN were absent. However, the narcotic did selectively reduce the inhibitory effect of LC conditioning stimulation on STN neurons without affecting that of the sensory ortex. Nalorphine partially antagonized this effect of the narcotic. A reduction in orthodromic spike number of STN neurons induced by intraventricular noradrenaline in reserpinized animals was unaltered by morphine treatment. These data demonstrate that morphine selectively interferes with LC-induced inhibition of STN neurons and in addition may block noradrenaline release from terminals of LC neurons.

Noradrenaline-mediated inhibition by locus coeruleus of spinal trigeminal neurons

Inhibitory effects of conditioning stimulation of the locus coeruleus (LC) on the neuron activity in spinal trigeminal nucleus (STN) were investigated in gallamine-immobilized cats. Field potentials of STN and spike potentials of single relay neurons in STN were orthodromically elicited by ipsilateral alveolar nerve stimulation and antidromically by stimulation of contralateral medial lemniscus. Conditioning stimuli were applied to LC and sensory cortex (SC) at various C-T intervals. In tracking experiments near the LC region, conditioning stimulation of LC itself produced the most pronounced decrease in amplitude of the STN field potentials. Orthodromic spikes of STN single neurons were significantly reduced by conditioning stimulation of LC as well as SC. In reserpine-treated animals, however, conditioning stimulation of LC failed to produce a decrease in the number of orthodromic spikes, while the inhibitory effect of SC conditioning stimulation remained unaffected. Under these circumstances, intravenous L-dopa and intraventricular noradrenaline reproduced an inhibitory effect of LC conditioning stimulation on orthodromic spike generation, while such an effect was not seen with either dopamine or serotonin. Antidromic spike was unaltered by any of these treatments. Histochemically, catecholamine fluorescence in LC was entirely eliminated after reserpine-treatment, but was restored after L-dopa injection. These results strongly suggest that noradrenaline released from the terminals of neurons originating in LC produces an inhibition of transmission in the STN relay neurons.

IMPAIRMENT BY 6-HYDROXYDOPAMINE OF LOCUSCOERULEUS-INDUCED MONOSYNAPTIC POTENTIALIN THE SPINAL TR IGEMINAL NUCLEUS'

All experiments were performed on cats immobilized with gallamine. In the rostral part of spinal trigeminal nucleus (STN), single fiber action potential with a consistent and short latency was elicited by electrical stimulation of the locus coe-ruleus (LC). When 2 mg of 6-hydroxydopamine (6-OHDA) dissolved in 5% ascorbic acid solution was applied into the lateral ventricle, the STN field potential produced by LC stimulation was reduced in amplitude within 20 hr. The STN potential elicited by trigeminal nerve stimulation, however, was unaffected until 24 hr after 6-OHDA. The drug also blocked the inhibitory effect of LC conditioning stimulation on the STN potential elicited by trigeminal nerve stimulation, whereas it did not modify the inhibitory effect of conditioning stimulation of the sensory cortex on the STN potential. Ascorbic acid solution, a solvent, affected neither the STN potential by LC simulation, nor the inhibitory effect of LC neurons on the STN potential elicited by trigeminal nerve stimulation. These results strongly suggest the existence of noradrenergic fiber from the LC to STN, through which inhibition of the STN neurons is produced.