Dual actions of N-butanol on electrical excitability of the molluscan neurons.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
C D Barnes
Publications and source records attributed to C D Barnes.
Effects of bestatin on the central cardiovascular regulatory mechanisms in the rat.
We evaluated the effects of bestatin, the specific aminopeptidase-B and leucine aminopeptidase inhibitor, on the central cardiovascular regulatory mechanisms in Sprague-Dawley rats anesthetized with pentobarbital sodium (40 mg/kg, i.p.). Intracerebroventricular injection of bestatin (100 or 200 nmol/5 microliters) consistently elevated the basal systemic arterial pressure and heart rate. At the same time, this degradative enzyme blocker increased the sensitivity of the baroreceptor reflex responses as well as the efficacy of the modulatory actions of the medullary nucleus reticularis gigantocellularis on these reflexes. We speculate that enhancing the tonic activities of the endogenous neuropeptides in the brain by protecting them from their catabolic enzymes may affect the central cardiovascular regulatory machinery by modifying the operations of the baroreceptor feedback controls and their modulatory mechanisms.
Animals↗
Serotonergic and non-serotonergic raphe neurons projecting to the feline lumbar and cervical spinal cord: a quantitative horseradish peroxidase-immunocytochemical study.
A quantitative study of raphe-spinal neurons and serotonergic neurons in 3 medullary raphe nuclei in the cat indicates that more than 80% of the raphe-spinal neurons that project to the spinal cord are serotonergic raphe-spinal neurons in each of the nuclei. More than 85% of the descending raphe-spinal neurons in the two caudal nuclei, nucleus raphe pallidus and nucleus raphe obscurus, are serotonergic, whereas 75% of the raphe-spinal neurons in the more rostrally placed nucleus raphe magnus contain serotonin (5-HT). These results are discussed in relation to descending systems containing both neuropeptides and 5-HT and collateralizing to several spinal segments.
Animals↗
Membrane excitability changes in hindlimb motoneurons induced by stimulation of the locus coeruleus in cats.
The present analysis describes the cellular mechanisms underlying the heightened membrane excitability of hindlimb flexor and extensor motoneurons upon stimulation of the locus coeruleus (LC) in unanesthetized, decerebrate cats. In a total of 73 cells, brief train stimuli to the LC at 50-300 microA intensity evoked one of 4 patterns of motoneuronal responses: a simple excitatory postsynaptic potential (EPSP) with weak trailing depolarization, a double-peak EPSP, an EPSP succeeded by a weak hyperpolarization, or a slow rising EPSP. As the initial dominant EPSP was a consistent finding among all cells and the ensuing potentials were variable in polarity, quantitative characterization was focused on the initial EPSP only. In all cells tested (n = 11), the LC-EPSP was accompanied by a decrease in input resistance. The excitatory LC action was further demonstrated by the consistent (n = 25 cells) motoneuron rheobase decrease when the latter was measured coincident with the summit of an LC-EPSP. Furthermore, the time course of the single-spike afterhyperpolarization became shortened during the LC conditioning stimuli (n = 16 motoneurons). Our data show that the descending LC action on motoneurons is typified by an EPSP accompanied by a net decrease in input resistance as well as a concurrent increase in motoneuron electrical excitability.
Animals↗
Suppression of the recurrent inhibitory pathway in lumbar cord segments during locus coeruleus stimulation in cats.
The present study revealed a consistent reduction of ventral root-induced recurrent inhibition of monosynaptic reflexes in both extensor (gastrocnemius-soleus) and flexor (common peroneal) motonuclei upon delivery of preconditioning stimuli to the locus coeruleus (LC) in decerebrate cats. The magnitudes of the LC-induced decrease in recurrent inhibition, functionally disinhibition, and of recurrent inhibition were significantly correlated. Direct recordings from Renshaw cells have indicated that LC conditioning stimuli cause a decrease in the number of spikes and the duration of firing in response to single antidromic (ventral root) volleys. These results suggest that the LC depression of the recurrent inhibitory pathway is attributed, in part at least, to inhibition of Renshaw cell activity.
Animals↗
Differential labeling of the vestibular complex following unilateral injections of horseradish peroxidase into the cat and rat locus coeruleus.
Following unilateral injections of horseradish peroxidase into the cat and rat locus coeruleus (LC), bilateral retrograde labeling was evident in all 4 vestibular nuclei. In both species, the major contributions of LC afferents arose from the ipsilateral rather than the contralateral vestibular nuclei. Quantitative analysis in the rat has indicated that approximately 90% of the total vestibular-LC projections originated from the ipsilateral vestibular nuclear complex, with 10% from the contralateral. The frequency distribution was in the order of lateral greater than medial greater than superior greater than inferior vestibular nuclei.
Animals↗
Brainstem sites of cholinergic actions on vestibulospinal reflex gain in cats.
Explore the source record for details and available documents.
Animals↗
Coerulospinal enhancement of repetitive firing with correlative changes in postspike afterhyperpolarization of cat spinal motoneurons.
The present study was aimed at determining if inputs from the locus coeruleus (LC) have any effect on repetitive firing of ventral horn motoneurons in cats. In hindlimb flexor and extensor motoneurons stimulated intrasomatically with current below the threshold for repetitive discharges, added LC-evoked excitatory post-synaptic potentials (EPSPs) were consistently found to produce repetitive firing, suggesting a lowering in the repetitive firing threshold attributable to excitatory LC inputs. With those extensor motoneurons showing episodic, self-sustained firing, LC-EPSPs introduced during the quiescent period were capable of starting a continuous discharge with rhythmic frequencies higher than the spontaneous activity. In some of these cells, intracellularly applied hyperpolarizing current was able to stop the spontaneous discharges. Subsequently, LC stimuli were found to reinitiate repetitive discharges, thus counteracting the ongoing suppression of the motoneurons. Quantitative analysis of the single-spike afterhyperpolarization (AHP) indicated a consistent reduction in its amplitude and time course (duration, time-to-peak, half-decay time) for flexor and extensor motoneurons in response to LC conditioning stimuli. Present results suggest an excitatory LC action on the repetitive discharges of cat motoneurons accompanied by a concurrent decrease in the amplitude and time course of the single-spike AHPs.
Animals↗
Presynaptic facilitatory action of locus coeruleus stimulation upon hindlimb sensory impulse transmission in decerebrate cats.
This study sought to delineate the presynaptic role of the locus coeruleus (LC) on hindlimb primary afferent terminals. Changes in presynaptic function in response to LC stimulation were assessed by measuring the dorsal root potential (DRP), interaction of LC- and peripherally-evoked DRPs, and intraspinal afferent terminal excitability. LC stimulation in unanesthetized, decerebrate cats produced a sequence of early and late positive DRPs succeeded by a small-sized negative DRP. Conditioning the negative DRPs elicited from individual hindlimb nerve branches with LC stimuli led to a decrease in test DRPs. Similarly, there was a predominant decrease in excitability in both large muscle and cutaneous afferent terminals. These data suggest a presynaptic role of the LC in augmenting afferent impulse transmission, presumably through inhibition of tonically active interneurons having axoaxonic contacts on primary afferents; functionally, presynaptic facilitation.
Afferent Pathways↗
Effects of microinjection of a cholinergic agonist into the locus coeruleus on the gain of vestibulospinal reflexes in decerebrate cats.
1. Experiments were performed in precollicular decerebrate cats to determine whether activation of locus coeruleus (LC) neurons elicited by local injection of the cholinergic agonist carbachol modifies the dynamic characteristics of responses of forelimb extensors to selective stimulation of labyrinth receptors resulting from roll tilt of the animal. 2. Injection of 0.1-0.4 microliter (usually 0.25 microliter) of carbachol at a concentration of 0.02-0.1 micrograms/microliter of sterile saline into the LC of one side, which slightly increased the tonic contraction of limb extensors ipsilateral to the side of the injection, greatly decreased the amplitude of the multiunit EMG response of the ipsilateral triceps brachii to animal tilt at 0.15 Hz, +/- 10 degrees. Correspondingly, the response gain of this forelimb extensor decreased. Moreover, a significant increase in phase lag of the responses was observed. These findings did not result from the increased postural activity, since they were still observed when the limb position was adjusted so that the spontaneous EMG activity remained constant throughout the experiments. 3. The changes in posture as well as in response characteristics of the forelimb extensor to labyrinth stimulation produced by carbachol injection appeared a few min after the injection and soon reached a plateau level which persisted for several hours before returning to the control levels. 4. The effects described above involved mainly, if not exclusively, the limbs ipsilateral to the side of the injection. However, the effects of local injection into the LC of one side could be reproduced on the contralateral side following injection into the LC of that side. 5. The increase in phase lag of the multiunit EMG responses of the triceps brachii to labyrinth stimulation appeared at a threshold lower than that required to decrease the response gain of this extensor muscle. These findings suggest that different neuronal populations within the LC complex, one projecting directly to the spinal cord, the other projecting indirectly through the pontine reticular formation, are involved in the control of phase angle and gain of the vestibulospinal reflexes, respectively. However, as soon as the threshold was reached the effects described above were dose-dependent. 6. Histological controls indicated that the structure responsible for the postural and reflex changes described above corresponded to the LC. In fact, postural and reflex changes opposite in sign to those described above were obtained when the same amount of carbachol was injected into the dorsal aspect of the pontine reticular formation (pRF) located immediately ventral to the LC.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Effects of microinjection of cholinergic agonists into the pontine reticular formation on the gain of vestibulospinal reflexes in decerebrate cats.
1. The question of which pontine neuronal groups and related receptors can mediate the cholinergic induction of the increased gain of vestibulospinal reflexes elicited by sinusoidal stimulation of labyrinth receptors was investigated by injecting in precollicular decerebrate cats either carbachol, which is a mixed muscarinic-nicotinic agonist, or bethanechol, which is a pure muscarinic agonist, via a cannula stereotaxically oriented in different pontine tegmental structures. 2. Injection of 0.1-0.2 microliter of carbachol solution (0.01-0.2 microgram/microliter of sterile saline) into the dorsal aspect of the pontine reticular formation (pRF), which slightly decreased the tonic contraction of limb extensors ipsilateral to the side of the injection, greatly increased the amplitude of the multiunit EMG response of the ipsilateral triceps brachii to roll tilt of the animal at 0.15 Hz, +/- 10 degrees, leading to selective stimulation of labyrinth receptors. Correspondingly, the response gain of the forelimb extensor to labyrinth stimulation increased. Moreover, a slight decrease in phase lead of the responses was observed. These findings were not attributable to decreased postural activity, since they were still observed when postural EMG activity was reflexly maintained by an increased static stretch of the muscle. No changes in the dynamic characteristics of the responses were observed in the contralateral triceps brachii. 3. The changes in posture as well as in response gain produced by the carbachol injection appeared suddenly, but partially declined to reach a plateau level which persisted for several hours before returning to the control level. Moreover, the magnitude of the effects increased in relation to the dose of the cholinergic agonist. 4. Histological controls indicated that the structure responsible for these postural and reflex changes was located in the dorsal aspect of the pontine tegmentum immediately ventral to the principal locus coeruleus (LC); this area corresponds to the peri-LC region and the surrounding pRF including the dorsal aspect of the central tegmental field. The effects were still obtained after chronic kainic acid lesioning of the gigantocellular area of the medulla. 5. An increase in gain of the vestibulospinal reflex which was as potent, dose-dependent, and site-specific as that previously observed with carbachol, appeared after injection of the pure muscarinic agonist bethanechol.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Anatomic and physiologic evaluation of a link between the nucleus reticularis gigantocellularis and nucleus ambiguous in the rat.
Localized microinjection of wheat germ agglutinin-conjugated horseradish peroxidase into the nucleus ambiguous (NA) of Sprague-Dawley rats retrogradely labeled neurons that were bilaterally located within the confine of the nucleus reticularis gigantocellularis (NRGC). These cells conformed with the Golgi description of cytoarchitectonic configurations and size distributions for neurons in this reticular nucleus. Furthermore, field potentials antidromically evoked at the NA by stimulating the vagus nerve were augmented by concurrent activations of bilateral NRGC sites that were themselves capable of eliciting hypotension and bradycardia. We conclude that the gigantocellular reticular nucleus may at least employ the cardiac vagal preganglionic neurons in the NA to exert its actions on the heart.
Animals↗
Facilitation of lumbar monosynaptic reflexes by locus coeruleus in the rat.
The present study was initiated to delineate whether species difference exists between cats and rats in the descending influence of locus coeruleus (LC) on spinal motoneuronal activity. In male Sprague-Dawley rats anesthetized with chloral hydrate (400 mg/kg, i.p.), localized activation of LC promoted an exclusive facilitation of lumbar spinal extensor and flexor monosynaptic reflexes (MSRs). Such LC-evoked potentiations may vary in degree (37.5-147.4%), duration (70.6-72.9 ms) and latency (3.0-5.5 ms) among different animals. While minimally affecting the control MSRs, the alpha 1-adrenoceptor blocker prazosin (20 micrograms/kg, i.v.) significantly antagonized the enhancing effect of the LC on MSRs, suggesting the participation of noradrenergic neurotransmission in the process. Since these results are in general agreement with previous observations from our laboratory on the cat, we conclude that the LC exerts similar facilitatory actions on both extensor and flexor motoneuron activity of the hindlimb in at least two animal species, rat and cat.
Animals↗
Stimulant action of ethanol on posttetanic potentiation of hindlimb monosynaptic reflexes.
Explore the source record for details and available documents.
Animals↗
Increased efficacy of antidromic and orthodromic activation of cat alpha motoneurons upon arrival of coerulospinal volleys.
The present study demonstrates the enhanced efficacy of impulse initiation among the hindlimb alpha motoneurons of flexor and extensor origins (n = 35) upon electrical stimulation of the locus coeruleus (LC) in decerebrate cats. When combined with the LC-evoked excitatory postsynaptic potential (EPSP), intracellular hyperpolarization-induced partial and total blocks of antidromic invasion were overcome, resulting in full-spike generation in all cells (n = 21). In three other cells, partial blocks, representing the motoneuron refractoriness resulting from double stimulation at close intervals, were relieved by the concomitant LC-EPSP. When an antidromic volley occurred at a time when the somadendritic (SD) membrane was near threshold, LC stimulation was shown to increase the probability of full-spike initiation as well as to shorten the initial segment (IS)-SD delay, suggesting a coerulospinal enhancement of the safety factor for IS-SD impulse conduction. When coincident with the LC-EPSPs, group Ia EPSPs of flexor and extensor origins were demonstrated to reach the threshold of discharging the cells (n = 4). In those cells exhibiting prominent depolarizing synaptic noise (n = 10), LC stimulation was sufficient to cause the cell to fire action potentials presumably by interacting with concomitant excitatory synaptic drive. The present results advocate that the descending LC excitatory drive has engaged in the action potential initiation process of the alpha motoneuron, facilitating its reaching the firing threshold during concurrent depressed membrane excitability as well as subthreshold converging inputs.
Action Potentials↗
A spinal projection of serotonergic neurons of the locus coeruleus in the cat.
A series of studies were done on adult cats to determine if the serotonergic neurons, reported in the nucleus locus coeruleus of that species, project to the lumbar spinal cord. The animals first were injected with 0.2 microliter of Evans blue into the ventral horn of the lumbar cord. Four days later the animals were perfused and prepared for fluorescence microscopic examination. The presence of Evans blue in both noradrenergic and serotonergic cells of the locus coeruleus was clearly evident in animals in which the injection was confined to the ventral horn area. In cat, the monoamine coerulospinal projection to the ventral horn of the lumbar cord arises from both norepinephrine and serotonin-containing neurons.
Animals↗
Bilateral lesions of the fastigial nucleus prevent the recovery of blood pressure following hypotension induced by hemorrhage or administration of endotoxin.
The present studies were undertaken to determine if bilateral lesions of the fastigial nuclei of the cerebellum would impair the recovery and maintenance of mean arterial blood pressure during hypotension caused by hemorrhage or administration of endotoxin. We had shown previously that cerebellectomy would produce such an impairment, and the fastigial nuclei were implicated as the specific area involved due to the known pressor response observed when they are stimulated electrically. Chloralose-anesthetized dogs were made hypotensive by administration of E. coli endotoxin or hemorrhage to 50 mm Hg and observed over the subsequent 3 h. Dogs with fastigial nucleus lesions had a significantly lower mean arterial pressure during both the recovery and maintenance phases when compared with intact animals under both hypotensive protocols. In the hemorrhage study, a significant number of lesioned animals died whereas none of the controls died. Lesion of the fastigial nuclei produced an impairment similar to that seen with cerebellectomy. It is concluded that the fastigial nuclei play an important role in the recovery of blood pressure following a hypotensive episode.
Animals↗
Cyclobenzaprine effects on locus coeruleus cells in tissue slice.
Tissue slices 400 mu thick were taken from the brain stem, at the level of the locus coeruleus, of 150-250 g Sprague-Dawley rats. Microelectrodes were placed in the locus coeruleus under visual control, and a cell whose discharge rate would decrease with microiontophoretic application of norepinephrine or clonidine was sought. Cyclobenzaprine (CBZ) was then introduced into the perfusion medium at a concentration equivalent to 1 mg/kg body weight of the whole animal. Discharge rates before and during CBZ administration were compared. The six cells with initial discharge rates between 2 and 10 Hz decreased firing with CBZ, whereas the four cells with initial rates between 0.5 and 1.5 Hz increased their rates with CBZ.
Action Potentials↗