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Results for “Locus Coeruleus”

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PubMed1979

NGF and anti-NGF: evidence against effects on fiber growth in locus coeruleus from cultures of perinatal CNS tissues.

The present study examines whether the developing noradrenergic neurons of locus coeruleus depend on endogenous nerve growth factor (NGF) for nerve fiber production and if exogenous NGF stimulates fiber growth in this nucleus, using a collagen gel tissue culture technique. Lucus coeruleus from perinatal rat brain was used in three culture experiments: (1) lucus coeruleus, parietal cerebral cortex, and the superior cervical ganglion, prepared from newborn rats and cultured in different sectors of the same dishes; (2) locus coeruleus and parietal cerebral cortex from 17-day-old rat fetuses cultured in the same manner, and (3) locus coeruleus from 17-day-old rat fetuses co-cultured with spinal, sympathetic and ciliary ganglia from 8-day chick embryos. Experiments 1 and 2 were run with and without addition of NGF and anti-NGF, experiment 3 with and without anti-NGF. Total fiber production in all cultured tissues was evaluated daily by dark field and phase contrast microscopy during 4 days. Adrenergic nerve fiber production was then studied in the same locus coeruleus and superior cervical ganglia from the rats by Falck-Hillarp fluorescence histochemistry. Locus coeruleus and cortex cerebri from fetal rats produced dense fiber halos in culture. Locus coeruleus from newborn rats produced considerably less fibers, newborn cortex only few fibers. Superior cervical ganglia from the same newborn animals produced no or almost no fibers. Addition of NGF was not able to stimulate fiber growth in locus coeruleus nor in cortex cerebri as observed both in the living cultures and by fluorescence microscopy. Likewise, addition of anti-NGF did not affect fiber production in the CNS areas. The negative results with NGF on newborn locus coeruleus and cortex cerebri were in sharp contrast to the strong, highly significant fiber growth response demonstrated by the superior cervical ganglion from the same animals cultured in the same dishes. The third experiment tested whether locus coeruleus in tissue culture contained or produced nerve growth factor or any one of the three chick embryo ganglia. No response whatsoever in these three ganglia was observed. It is concluded that the developing locus coeruleus area does not contain or produce NGF, does not depend on NGF for fiber production, and is not stimulated by exogenous NGF.

Animals↗

PubMed1995

Galanin induces a hyperpolarization of norepinephrine-containing locus coeruleus neurons in the brainstem slice.

Galanin applied in the bath or by micropipette directly on to locus coeruleus neurons in an in vitro slice preparation caused a hyperpolarization accompanied by a small decrease in membrane resistance. Immunohistochemical staining of intracellularly filled neurons indicated that the effect of galanin was exerted on norepinephrine neurons of the locus coeruleus. The galanin effect was variable in amplitude and duration and often showed desensitization, with subsequent applications producing a smaller response. When cells were exposed to tetrodotoxin or tetrodotoxin/low calcium media, the galanin response was still present. Under voltage clamp galanin application caused a net outward current that did not reverse in normal potassium concentrations; however, by increasing extracellular potassium concentrations the net outward current was reversed and the reversal potential shifted to a less negative potential. The response to galanin was identical when either KCl or KAc was used as the intracellular electrode solution. Tetraethylammonium chloride significantly reduced or abolished the response to galanin in most cells, although in a few cells the galanin response was not affected. Glibenclamide, a blocker of ATP-sensitive potassium channels, did not affect the galanin hyperpolarization. In addition, diazoxide had no effect on the membrane properties of locus coeruleus neurons. These results demonstrate that galanin exerts its inhibitory effect in the locus coeruleus via an increase in K+ conductance; however, not via the pancreatic type of ATP-sensitive K+ channels. Cryostat sections of the locus coeruleus incubated in 125I-labeled galanin revealed binding sites in the locus coeruleus at all levels. Sections of the locus coeruleus processed for ultrastructural immunocytochemistry showed galanin immunoreactivity in many neuronal somata and dendritic processes within the nucleus, confirming earlier evidence for the coexistence of galanin and noradrenaline in locus coeruleus neurons. Galanin-immunoreactive soma and dendrites in the locus coeruleus less frequently received galanin-immunoreactive synapses of axonal origin. These findings suggest that endogenous galanin in the locus coeruleus is mainly released from noradrenaline galanin somata and/or dendrites to act on autoreceptors or on receptors on adjacent neurons.

Animals↗

PubMed1983

Participation of the nucleus locus coeruleus in DOCA-salt hypertensive rats.

The locus coeruleus was subjected to biphasic electrical stimulation, and a group of deoxycorticosterone acetate (DOCA)-salt hypertensive rats revealed a greater pressor response than a group of normotensive control rats. The pressor threshold current (i.e. minimum current to raise the arterial pressure by 10 mm Hg) of DOCA-salt hypertensive rats was also lower. The threshold current was low even in the prehypertensive stage of DOCA-salt treated rats. During arterial pressure fall, the pressor threshold current lowered only in normotensive rats and neither group underwent a change during pressure rise. These data indicated that the locus coeruleus had a pressor role and it had been accelerated in DOCA-salt treated rats before hypertension was evident. Following bilateral electrical lesions of the locus coeruleus no significant differences were observed in the arterial pressure changes, while vascular reactivity to norepinephrine did not differ between the two groups. The results suggest that the locus coeruleus may be involved in the development of hypertension but may not be important in the maintenance of it.

Animals↗

PubMed1988

Evidence for functional contact between cografted locus coeruleus and spinal cord in oculo: electrophysiological studies.

The functional consequences of the locus coeruleus innervation of the spinal cord are not yet clearly understood. In a recent histological study it was shown that intraocular spinal cord grafts will become innervated by tyrosine hydroxylase-positive nerve fibers from a cografted locus coeruleus. In the present study we use this intraocular model of the descending coeruleo-spinal pathway to investigate functional contact between locus coeruleus and the spinal cord. We have pharmacologically characterized the receptor mediation of norepinephrine-induced, as well as locus coeruleus-mediated depressions of spinal cord neurons grafted in oculo. We found that electrical stimulation of the locus coeruleus part of the double grafts predominantly caused an inhibition of cografted spinal cord neurons. Norepinephrine-induced inhibition of the firing rate of single grafted spinal cord neurons was antagonized by phentolamine, an alpha-adrenergic antagonist, but was unaffected by timolol, a beta-adrenergic antagonist. Similarly, inhibition of the firing rate of grafted spinal cord neurons by stimulation of cografted locus coeruleus was antagonized by phentolamine but not by timolol. Interestingly, single spinal cord grafts were more sensitive to the depressant effects of perfused norepinephrine than was the spinal cord cografted with locus coeruleus. We conclude that spinal cord grafts can be functionally innervated by cografted locus coeruleus and that the noradrenergic inputs to spinal cord from cografted locus coeruleus are alpha-adrenergically mediated. Furthermore, the postsynaptic receptors in single spinal cord grafts appear to be supersensitive to norepinephrine application.

Action Potentials↗

PubMed1994

QX-314 blocks the potassium but not the sodium-dependent component of the opiate response in locus coeruleus neurons.

Opiates hyperpolarize locus coeruleus neurons by simultaneously opening K+ channels and turning off a resting Na(+)-dependent inward current. Intracellularly applied QX-314 reduced the opiate current to approximately 40% of the control and the residual current did not reverse near EK, suggesting lack of a significant K+ component. Replacement of Na+ virtually abolished the residual opiate response. Thus, QX-314 blocks the K+ but not the Na(+)-dependent component of the opiate-induced outward current in LC neurons.

Anesthetics, Local↗

PubMed1977

Suppression of an eplieptiform type of electrocortical activity in the rat by stimulation in the vicinity of locus coeruleus.

Stimulation of the locus coeruleus, or in the vicinity of this nucleus or of its ascending tracts, could markedly suppress the appearance of epileptiform-like ECoG bursts. The latter were induced in rats by a subconvulsive dose of pentylenetetrazol. Electrode sites were identified histologically. A unilateral stimulus suppressed bursts bilaterally. An individual burst already in progress could be aborted, stopping within less than 0.5-1 sec after onset of a stimulus train. The antiepileptiform actions occurred with no evidence of any desynchronizing effect of the stimulus on the resting ECoG; they appear to be different in sites of origin and nature from those reported for stimulation of the reticular activating system. It is proposed that stimulation of the ascending noradrenergic system in the brain stem may limit the development and spread of hyperexcitatory, epileptiform states.

Animals↗

PubMed1999

Relationship between locus coeruleus discharge rates and rates of norepinephrine release within neocortex as assessed by in vivo microdialysis.

The relationship between discharge rates of locus coeruleus noradrenergic neurons and rates of norepinephrine release was examined in the anesthetized rat. Neuronal discharge rates of locus coeruleus neurons were altered and quantified using a combined recording-infusion probe. Peri-locus coeruleus infusions of either the cholinergic agonist, bethanechol, or the alpha2-agonist, clonidine, were used to enhance or suppress neuronal discharge activity, respectively. Alterations in concentrations of extracellular norepinephrine within the prefrontal cortex were determined using in vivo microdialysis and high-pressure liquid chromatography with electrochemical detection. A linear relationship between locus coeruleus activity and norepinephrine dialysate concentration was observed between complete suppression of locus coeruleus discharge activity and approximately 300-400% of basal discharge levels (1.58+/-0.29 Hz). Above these levels, increases in locus coeruleus discharge rates were not accompanied by similar increases in dialysate norepinephrine concentrations. In general, neither activation nor suppression of locus coeruleus neuronal discharge rates appeared to alter the relationship between discharge activity and norepinephrine efflux during subsequent epochs. The one exception to this was observed during recovery from relatively high-magnitude locus coeruleus activation. In two out of three cases in which locus coeruleus discharge rates were increased greater than 450%, a recovery of norepinephrine concentrations to basal levels occurred more quickly than the recovery of locus coeruleus neuronal discharge rates to basal levels. Although limited, these latter observations suggest that dysregulation of norepinephrine release may occur following sustained activation of locus coeruleus at the highest rates examined, which may mimic those associated with intense arousal or stress.

Animals↗

PubMed2006

Specificity of prenatal cocaine on inhibition of locus coeruleus neurite outgrowth.

Prenatal cocaine exposure induces alterations in attentional function that presumably involve locus coeruleus noradrenergic neurons and their projections. Previous reports indicate that embryonic rat locus coeruleus neurons exposed to cocaine, both in vitro and in vivo, showed in decreased cell survival and inhibition of neurite outgrowth, and that the effects were most deleterious during early gestation. The present study performed in vitro addressed the specificity of the inhibitory effects of cocaine by comparing locus coeruleus neurite formation and extension to that of dopaminergic substantia nigra neurons following exposure to a physiologically-relevant dose of cocaine (500 ng/ml, two times a day, for four days) during peak neuritogenesis. Following cocaine treatment, immunocytochemistry (anti-norepinephrine antibody to locus coeruleus; anti-tyrosine hydroxylase antibody to substantia nigra) and image analysis were performed to measure a variety of neurite outgrowth parameters. For locus coeruleus neurons, cocaine treatment decreased the 1) number of cells initiating neurites [P<0.001], 2) mean number [P<0.05] and length of neurites [P<0.0001], 3) mean number [P<0.0016] and length of branched neurites [P<0.0006], and 4) mean length of the longest neurites [P<0.0001]. In comparison, substantia nigra neurons were not significantly affected by cocaine for any of the parameters examined. More importantly, a significant interaction between cocaine treatment and brain region was observed [P<0.0002] indicating greater vulnerability of locus coeruleus, relative to substantia nigra neurons, to cocaine exposure. These data support our hypothesis that cocaine targets the noradrenergic system by negatively regulating locus coeruleus neuronal outgrowth, which likely affects pathfinding, synaptic connectivity, and ultimately attentional behavior in cocaine-exposed offspring.

Animals↗

PubMed1986

Evidence for self- and neighbor-mediated postactivation inhibition of locus coeruleus neurons.

Activation of locus coeruleus (LC) neurons is typically followed by inhibition of impulse activity lasting hundreds of ms. Previous studies have implicated two possible mechanisms for this postactivation inhibition: collateral synaptic interactions among LC neurons; and spike-induced, calcium-activated potassium conductance in the soma-dendritic membrane of LC cells. In the present study, antidromic or sensory stimuli were presented at near-threshold intensities for activation of LC neurons. A special computer program accumulated activity for trials yielding driven responses separately from that for trials of identical stimuli during the same train that failed to evoke activity. We found significant inhibition of LC impulse activity for antidromic or sensory stimuli that failed to excite the recorded cell as well as for stimuli that activated the recorded cell. The former result precludes an essential role of intrinsic inhibitory membrane currents (e.g. calcium-activated potassium conductance) in generating postactivation inhibition. Administration of the alpha antagonist piperoxane reduced the magnitude of inhibition on both driven and non-driven trials. Our findings indicate that inhibition on non-driven trials appears to be a synaptically mediated phenomenon, perhaps reflecting norepinephrine released from neighboring LC neurons that are activated. Furthermore, our data support the presence of a spike-dependent mechanism that also contributes substantially to postactivation inhibition in these cells. Thus, the overall results indicate the presence of two intracoerulear mechanisms that mediate postactivation inhibition characteristic of noradrenergic LC neurons.

Adrenergic Fibers↗

PubMedDate not supplied

Expression of connexins during development and following manipulation of afferent input in the rat locus coeruleus.

Synchronous activity of locus coeruleus (LC) neurons during early postnatal development is regulated, in part, by electrotonic coupling. Connexin (Cx) proteins that make up gap junction channels are localized to both neurons and glia in the LC during this period. In adult rats, however, synchrony exists only under certain experimental conditions. The expression of Cx proteins was examined using western blot analysis at several developmental time points. Immunoblot analysis revealed little to no expression of Cx26 while Cx32, Cx43 and Cx36 were present at all time points examined. A progressive increase in Cx43 was identified from the first postnatal week through adulthood. Immunocytochemical detection of Cx36 and Cx43 in adult LC showed that Cx36 was associated with neuronal processes while Cx43 was localized to glia. In adult LC, in vitro intracellular recordings combined with neurobiotin injections confirmed the presence of gap junctional communication albeit to a lesser extent than in early postnatal periods. The degree to which synaptic inputs to LC neurons impact on Cx protein expression was also evaluated. Samples of the LC from rats that received an electrolytic lesion of the amygdala were processed for western blot analysis of Cx36 and Cx43. The predominantly neuronal Cx36 exhibited an increase in expression while the glial Cx43 was unchanged. The present results indicate that, despite subtype-specific changes during development, several Cx proteins are expressed in the adult LC. In addition, manipulating afferent input to the LC, in adult rats, results in increases in neuronal Cx protein levels but not in glial Cx levels suggesting that altering synaptic inputs to the LC may alter synchronous activity in noradrenergic neurons.

Afferent Pathways↗

PubMed1998

Tachykinin NK1 receptor antagonists enhance stress-induced c-fos in rat locus coeruleus.

These experiments tested the hypothesis that substance P neurotransmission at tachykinin NK1 receptors in the locus coeruleus is involved in stress-induced activation of the locus coeruleus, using c-fos as an index of activation. Selective tachykinin NK1 receptor antagonists administered systemically did not result in substantial locus coeruleus c-fos expression. Restraint stress resulted in a large number of locus coeruleus c-fos expressing cells. Administration of two selective tachykinin NK1 receptor antagonists prior to restraint resulted in an increase in the number of locus coeruleus c-fos expressing cells, compared to restraint alone. These results suggest that the enhanced c-fos expression observed in response to tachykinin NK1 receptor antagonists combined with stress, could be due to the blockade of tachykinin NK1 receptor-mediated activity at sites other than the locus coeruleus, resulting in an overall activation of the locus coeruleus.

Acetamides↗

PubMed2000

Effects of inescapable shock and conditioned fear on the release of excitatory and inhibitory amino acids in the locus coeruleus.

We investigated the importance of endogenous amino acids in the locus coeruleus in inescapable electric shock and conditioned fear. In naive rats and in rats exposed to noise (N), light (L) and electric shock (S) or to N + L only, the locus coeruleus was superfused with artificial cerebrospinal fluid through a push-pull cannula and the release of GABA, taurine, glutamate, aspartate, serine and glutamine was determined in the superfusate by HPLC after derivatization with o-phthaldialdehyde. Locomotor activity, arterial blood pressure and heart rate were telemetrically monitored. The placement of naive rats or conditioned rats from their home cage to a chamber provided with a grid-floor for shock virtually did not change the release rates of the amino acids in the locus coeruleus. Motility was enhanced in naive and conditioned rats to a similar extent. Blood pressure and heart rate were enhanced in conditioned rats only. Exposure to N + L + S for 5 min greatly enhanced the release rates of all determined amino acids in the locus coeruleus. In conditioned rats the increase in release of most amino acids lasted longer than in naive rats. Electric shock also enhanced motility, blood pressure and heart rate. In conditioned rats, motility and cardiovascular changes were more pronounced and/or lasted longer than in naive rats. Exposure of conditioned rats to the conditioned stimuli N + L for 5 min led to an increased release of taurine and aspartate. The enhanced release of taurine lasted 30 min. Exposure to N + L did not affect the release rates of amino acids in naive rats. N + L did not influence motility but arterial blood pressure and heart rate were elevated in conditioned rats. The findings show that inescapable electric shock enhances the release of several amino acids in the locus coeruleus, while conditioned fear selectively increases the outflow of taurine and aspartate. Moreover, conditioned fear prolongs the response of excitatory and inhibitory amino acids to electric shock. The results suggest that an excitatory amino acid (aspartate) and an inhibitory amino acid (taurine) of the locus coeruleus are implicated in conditioned fear.

Amino Acids↗

PubMed1977

Ascending projections of the locus coeruleus in the rat. II. Autoradiographic study.

The ascending projections of the locus coeruleus were studied using an autoradiographic method. The major projection of locus coeruleus neurons ascends in a dorsal pathway traversing the midbrain tegmentum in a position ventrolateral to the periaqueductal gray. At the caudal diencephalon the locus coeruleus axons descend to enter the medial forebrain bundle at a caudal tuberal hypothalamic level. They are jointed in the medial forebrain bundle by a much smaller locus coeruleus projection which takes a ventral course through the midbrain tegmentum and enters the medial forebrain bundle via the mammillary peduncle and ventral tegmental area. Terminal projections are evident in the midbrain to the periaqueductal gray, tegmentum and raphe nuclei. There are widespread projections to the dorsal thalamus. The heaviest of these are to the intralaminar nuclei, the anteroventral and anteromedial nuclei, the dorsal lateral geniculate and the paraventricular nucleus. In the hypothalamus the largest projections are to the lateral hypothalamic area, periventricular nucleus, supraoptic nucleus and paraventricular nucleus. As the locus coeruleus projection ascends in the medial forebrain bundle, fibers leave it to traverse the lateral hypothalamus and zona incerta and enter the internal capsule, the ventral amygdaloid bundle and ansa peduncularis. These appear to terminate in the amygdaloid complex and, via the external capsule, in the lateral and dorsal neocortex. At the level of the septum 4 projections are evident. One group of fibers enters the stria medullaris to terminate in the paraventricular nucleus and habenular nuclei. A second group joins the stria terminalis to terminate in the anygdaloid complex. The third group turns into the diagonal band and medial septum; some fibers terminate in the septal nuclei and others continue into the fornix to termimate in hippocampus. A large component continues around the corpus callosum into the cingulum to terminate in the cingulate and adjacent neocortex, the subiculum and hippocampus. The remaining fibers continue rostrally in the medial forebrain bundle to terminate in olfactory forebrain and frontal neocortex. Commissural projections arise at 4 locations. The first decussation occurs in the dorsal tegmentum just below the central gray rostral to the locus coeruleus. The crossing fibers enter the contralateral dorsal bundle. A second group of fibers leaves the ipsilateral dorsal pathway, crosses in the posterior commissure and enters the contralateral dorsal pathway at the level. The third commissural projection arises more rostrally and crosses in the dorsal supraoptic commissure to enter the contralateral medial forebrain bundle. The fourth commissural projection is through the anterior commissure. The termination of the contralateral projection appears similar to that of the ipsilateral projection.

Afferent Pathways↗

PubMed1992

Inhibition of noradrenergic locus coeruleus neurons by C1 adrenergic cells in the rostral ventral medulla.

Recent anatomical and physiological experiments indicate that the nucleus locus coeruleus receives a predominant excitatory amino acid input, as well as a substantial inhibitory input, from the nucleus paragigantocellularis in the ventrolateral medulla. To determine whether C1 adrenergic neurons are involved in the inhibitory projection, the effects of the alpha-2 adrenoceptor antagonist, idazoxan, on inhibitory responses of locus coeruleus neurons to paragigantocellularis stimulation were characterized in the rat. Intravenous administration of idazoxan (0.2-1 mg/kg) attenuated paragigantocellularis-evoked inhibition, and often revealed an underlying weak excitation. Intraventricular administration of kynurenate, an excitatory amino acid antagonist, eliminated excitation from paragigantocellularis and disclosed an underlying inhibitory response in many locus coeruleus neurons that were previously excited by paragigantocellularis stimulation. These results revealed that about 90% of locus coeruleus neurons receive inhibition from the paragigantocellularis. Intravenous idazoxan significantly reduced such paragigantocellularis-evoked inhibition, completely blocking this response in three of eight locus coeruleus cells tested. Idazoxan was much more potent when locally infused into the locus coeruleus. Local infusion of idazoxan (0.1-2.5 ng) into locus coeruleus produced a dose-dependent decrease of paragigantocellularis-evoked inhibition and completely blocked the inhibition in 10/33 locus coeruleus neurons, indicating that the site of idazoxan action was in the locus coeruleus. These results extend our previous anatomical studies of adrenergic input to locus coeruleus, and indicate that C1 adrenergic neurons in the paragigantocellularis provide a direct inhibitory input to the great majority of locus coeruleus noradrenergic neurons. In addition, this is the first report of a neuronal response to activation of C1 adrenergic cells indicating that these neurons are strongly inhibitory when acting at alpha-2 receptors in vivo.

Adrenergic alpha-Antagonists↗

PubMed1999

Evidence that 3,3',5-triiodothyronine is concentrated in and delivered from the locus coeruleus to its noradrenergic targets via anterograde axonal transport.

Recent immunohistochemical studies of rat brain triiodothyronine reveal heaviest localization in locus coeruleus perikarya. The cellular distribution is similar to that observed in concomitant studies of tyrosine hydroxylase immunohistochemistry: heavy clumps of immunoreactive triiodothyronine are distributed within locus coeruleus cytosol and in cell processes, leaving cell nuclei unstained. At the same time, in locus coeruleus targets, cell nuclei as well as surrounding neuropil are prominently triiodothyronine labeled. These observations, combined with diverse evidence linking thyroid hormone with norepinephrine at many levels of physiological and pathophysiological function, led to the hypothesis that the locus coeruleus binds and accumulates triiodothyronine and delivers the hormone via anterograde axonal transport to postsynaptic locus coeruleus targets, where nuclear triiodothyronine receptors are densely concentrated. Furthermore, the hypothesis predicts that destruction of locus coeruleus nerve terminals would interrupt this neural route of triiodothyronine delivery and prevent or reduce triiodothyronine labeling of nuclear receptors in noradrenergic target cells. To test this formulation, we gave the specific locus coeruleus lesioning agent, N-(2-chloroethyl)-N-2-bromobenzylamine hydrochloride (DSP-4), to adult male rats and examined their brains three, five and seven days thereafter by triiodothyronine and, in alternate sections, tyrosine hydroxylase immunohistochemistry. Treatment with DSP-4 resulted in specific and selective reduction in tyrosine hydroxylase and triiodothyronine immunohistochemical labeling in cell nuclei and in nerve cell processes within the neuropil of the hippocampus and cerebral cortex at all time periods examined. The results demonstrate that full occupancy of locus coeruleus target cells by triiodothyronine requires the presence of intact locus coeruleus projections and supports the proposal that, like norepinephrine, triiodothyronine delivery to noradrenergic targets occurs through delivery by locus coeruleus terminals. These findings provide strong support for earlier proposals that triiodothyronine functions as a co-transmitter with norepinephrine in addition to or as part of its genomic role in the cells receiving noradrenergic innervation.

Adrenergic Fibers↗

PubMed1987

The mode of projections of single locus coeruleus neurons to the cerebral cortex in rats.

Axonal distributions of single locus coeruleus neurons within the cerebral cortex were examined with antidromic stimulation technique combined with cortical lesions (frontal lobotomy and lobectomy). In urethan-anesthetized rats, stimulating electrodes were implanted in 10 points extending over nearly the entire cerebral cortex, and antidromic responses of single locus coeruleus neurons to stimulation of these stimulus sites were analysed. Fifty percent of locus coeruleus neurons examined were activated antidromically from at least one cortical point in the cerebral cortex. The pattern and extent of axonal distributions of single locus coeruleus neurons in the cortex appeared to vary from cell to cell. From the results obtained in rats with the cortical lesions, it is concluded that in addition to locus coeruleus neurons with intracortical axons running from rostral to caudal, there are the neurons projecting to the occipital cortex without innervating the frontal cortex and those projecting simultaneously to the frontal and occipital cortex with two axonal branches. There was no topographic order between the recording sites within the locus coeruleus and the projection sites in the cortex.

Afferent Pathways↗

PubMed1998

Influence of excitatory amino acids on basal and sensory stimuli-induced release of 5-HT in the locus coeruleus.

1. The interactions between 5-hydroxytryptaminergic neurones and excitatory amino acid utilizing neurones were studied in the locus coeruleus of conscious, freely moving rats. The locus coeruleus was superfused with artificial cerebrospinal fluid through a push-pull cannula and 5-hydroxytryptamine (5-HT) was determined in the superfusate that was continuously collected in time periods of 10 min. 2. Superfusion of the locus coeruleus with the NMDA receptor antagonist AP5 (10 microM), kynurenic acid (1 mM), or the AMPA/kainate receptor antagonist DNQX (10 microM) reduced the 5-HT release in the locus coeruleus. 3. Superfusion with the agonists NMDA (50 microM), kainic acid (50 microM) or AMPA (10 microM) enhanced the release rate of 5-HT. AP5 (10 microM) blocked the stimulant effect of NMDA, while tetrodotoxin (1 microM) failed to influence the NMDA-induced release of 5-HT. In the presence of 10 microM DNQX, the releasing effect of 50 microM kainic acid was abolished. 4. Pain elicited by tail pinch, as well as noise-induced stress, increased the release of 5-HT. Superfusion of the locus coeruleus with 10 microM AP5 reduced the tail pinch-induced 5-HT release. AP5 (10 microM) did not affect the noise-induced release of 5-HT which was reduced, when the locus coeruleus was superfused simultaneously with this concentration of AP5 and 1 microM kynurenic acid. DNQX (10 mM) failed to influence the release of 5-HT induced by tail pinch or noise. 5. The findings suggest that 5-hydroxytryptaminergic neurones of the locus coeruleus are tonically modulated by excitatory amino acids via NMDA and AMPA/kainate receptors. The release of 5-HT elicited by tail pinch and noise is mediated to a considerable extent through endogenous excitatory amino acids acting on NMDA receptors, while AMPA/kainate receptors are not involved in this process.

Acoustic Stimulation↗

PubMed1993

Development of dopamine-beta-hydroxylase-positive fiber innervation in co-cultured hippocampus-locus coeruleus organotypic slices.

Development of the noradrenergic innervation of the rat hippocampus by the nucleus locus coeruleus was examined immunohistochemically in the roller tube organotypic cultured slice preparation. Slices of rat hippocampus and locus coeruleus were co-cultured on glass coverslips for 2-6 weeks and evaluated for the presence of dopamine-beta-hydroxylase (DBH) and tyrosine hydroxylase (TH) immunoreactive cells and fibers. Large, multipolar DBH- and TH-positive cells were visible within the locus coeruleus; an occasional cell appeared near or just within co-cultured hippocampal tissue and in connecting fiber tracts. DBH-positive cells tended to concentrate near the edges of locus coeruleus tissue. Locus coeruleus slices cultured alone showed little indication of fiber outgrowth in any direction. In co-cultures, however, beaded DBH- and TH-positive fibers were directed toward the hippocampus. The majority of these fibers entered the hippocampus in the hilar/CA3 region and formed extensive collateral branches. Light microscopy suggests that DBH-positive fiber growth was densest at or near the pyramidal cell layer in CA3b and CA3c and in the infragranular region of the dentate hilus. This pattern of noradrenergic innervation of hippocampus by co-cultured locus coeruleus in vitro appears very similar to the pattern established in vivo (see Moudy et al., companion article, this issue).

Animals↗