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P d'Ascanio

Publications and source records attributed to P d'Ascanio.

At least 19 recordsLinked to original sources
PubMed2004

Gene expression in autonomic areas of the medulla and the central nucleus of the amygdala in rats during and after space flight.

During space flight astronauts show vestibular-related changes in balance, eye movements, and spontaneous and reflex control of cardiovascular, respiratory and gastrointestinal function, sometimes associated with space motion sickness. These symptoms undergo compensation over time. Here we used changes in the expression of two immediate-early gene (IEG) products to identify cellular and molecular changes occurring in autonomic brainstem regions of adult male albino rats killed at different times during the Neurolab Space Mission (STS-90). Both direct effects of gravitational changes, as well as indirect effects of gravitational changes on responses to light exposure were examined. Regions under the direct control of vestibular afferents such as the area postrema and the caudal part of the nucleus of the tractus solitarius (NTSC) were both directly and indirectly affected by gravity changes. These areas showed no changes in the expression of IEG products during exposure to microgravity with respect to ground controls, but did show a significant increase 24 h after return to 1 G (gravity). Exposure to microgravity significantly inhibited gene responses to light exposure seen after return to 1 G. A similar direct and indirect response pattern was also shown by the central nucleus of the amygdala, a basal forebrain structure anatomically and functionally related to the NTS. The rostral part of the NTS (NTSR) receives different afferent projections than the NTSC. This region did not show any direct gravity-related changes in IEG expression, but showed an indirect effect of gravity on IEG responses to light. A similar pattern was also obtained in the intermediate reticular nucleus and the parvocellular reticular nucleus. Two other medullary reticular structures, the dorsal and the ventral medullary reticular nuclei showed a less well defined pattern of responses that differed from those seen in the NTSC and NTSR. The short- and long-lasting molecular changes in medullary and basal forebrain gene expression described here are thought to play an important role in the integration of autonomic and vestibular signals that ultimately regulate neural adaptations to space flight.

Amygdala↗
PubMed2002

Gene expression in rat vestibular and reticular structures during and after space flight.

Space flight produces profound changes of neuronal activity in the mammalian vestibular and reticular systems, affecting postural and motor functions. These changes are compensated over time by plastic alterations in the brain. Immediate early genes (IEGs) are useful indicators of both activity changes and neuronal plasticity. We studied the expression of two IEG protein products [Fos and Fos-related antigens (FRAs)] with different cell persistence times (hours and days, respectively) to identify brainstem vestibular and reticular structures involved in adaptation to microgravity and readaptation to 1 G (gravity) during the NASA Neurolab Mission (STS-90). IEG protein expression in flight animals was compared to that of ground controls using Fisher 344 rats killed 1 and 12 days after launch and 1 and 14 days after landing. An increase in the number of Fos-protein-positive cells in vestibular (especially medial and spinal) regions was observed 1 day after launch and 1 day after landing. Fos-positive cell numbers were no different from controls 12 days after launch or 14 days after landing. No G-related changes in IEG expression were observed in the lateral vestibular nucleus. The pattern of FRA protein expression was generally similar to that of Fos, except at 1 day after landing, when FRA-expressing cells were observed throughout the whole spinal vestibular nucleus, but only in the caudal part of the medial vestibular nucleus. Fos expression was found throughout the entire medial vestibular nucleus at this time. While both Fos and FRA expression patterns may reflect the increased G force experienced during take-off and landing, the Fos pattern may additionally reflect recent rebound episodes of rapid eye movement (REM) sleep following forced wakefulness, especially after landing. Pontine activity sources producing rhythmic discharges of vestibulo-oculomotor neurons during REM sleep could substitute for labyrinthine signals after exposure to microgravity, contributing to activity-related plastic changes leading to G readaptation. Reticular structures exhibited a contrasting pattern of changes in the numbers of Fos- and FRA-positive cells suggestive of a major influence from proprioceptive inputs, and plastic re-weighting of inputs after landing. Asymmetric induction of Fos and FRAs observed in some vestibular nuclei 1 day after landing suggests that activity asymmetries between bilateral otolith organs, their primary labyrinthine afferents, and vestibular nuclei may become unmasked during flight.

Adaptation, Physiological↗
PubMed2002

Short-term (Fos) and long-term (FRA) protein expression in rat locus coeruleus neurons during the neurolab mission: contribution of altered gravitational fields, stress, and other factors.

Changes in immediate-early gene (IEG) expression during and after space flight were studied in the rat locus coeruleus (LC) during the NASA Neurolab mission. The LC sends widespread projections throughout the brain and releases the neuromodulator norepinephrine. LC neurons respond to natural vestibular stimulation; their firing rate also increases during waking and decreases or ceases during sleep. LC neurons express IEGs such as c-fos after activation. Adult male albino Fisher 344 rats were killed at four mission time points, and the number of Fos- and Fos-related antigen (FRA)-positive LC cells were counted in flight and ground-based control rats. Half of the subjects at each time point were exposed to light for 60 min prior to killing to standardize their sleep-waking state. FRA-expressing cells were more numerous than Fos-expressing cells in both flight- and ground-based subjects. The difference between FRA- and Fos-expressing cells within individuals was significantly larger 24 h after landing in subjects exposed to both space flight and light pulse than in all other subjects at any mission time point. Fos and FRA responses scaled in proportion to the maximum response observed in any single individual showed similar patterns of variation. Analysis of the scaled and combined responses showed that LC IEG levels responded to both gravity changes and light pulses. Subjects exposed to either single stimulus had equivalent responses, significantly greater than those of control subjects maintained in dim light. The combination of gravity change and light pulse gave significantly higher LC responses than either stimulus alone 24 h after takeoff, and to a lesser extent after 12 days in space; the highest responses were obtained 24 h after landing. By 14 days after landing, animals exposed to space flight and light pulse responded no differently than ground-based subjects. No difference in LC IEG expression was clearly attributable to changes in the sleep-waking state of subjects. Activity of noradrenergic LC neurons has been previously shown to modulate IEG expression in target structures. The increased IEG LC activity (seen most especially 24 h after landing) may reflect large-scale activation of noradrenergic neurons that may serve as a trigger for molecular changes in target structures, and be critical for adaptation to gravity changes.

Adaptation, Physiological↗
PubMed2001

Immediate early gene expression in the vestibular nuclei and related vegetative areas in rats during space flight.

Changes in neuronal activity resulting in somatic and vegetative deficits occur during different space flight conditions. Immediate early genes (IEGs: c-fos and Fos-related antigen [FRA]) are useful indicators of changes in neuronal activity and plasticity. They are induced within minutes of several extracellular stimulations, while the corresponding proteins persist for hours (Fos) or days (FRAs). Changes in IEG expression are likely to contribute to adaptation to microgravity and readaptation to the terrestrial environment. During the NASA Neurolab Mission (STS-90), changes in IEG expression were studied in adult male albino rats (Fisher 344) sacrificed at flight day (FD) 2 (24 h after launch), FD14 and at similar time points after re-entry (R + 1, 24 h after re-entry, and R + 13). These time points were chosen to maximize the probability of detecting changes in IEG expression related to changes in gravitational fields occurring during the mission, e.g. (i) increase in gravitational force from 1 to 3 g during the launch, before reaching about 0 g at FD2; (ii) adaptation to 0 g at FD14; (iii) increase in gravity from 0 to approximately 1.5-1.8 g before reaching 1 g at R + 1; and (iv) readaptation to 1 g at R + 13. Fos- and FRA-positive cells were identified in the brainstem of flight rats and ground-based controls using immunocytochemistry. With respect to control rats, the number of labeled cells increased in flight animals in the medial and spinal vestibular nuclei (but not in the lateral vestibular nucleus) at FD2, decreased at FD14, greatly increased at R + 1 and returned to baseline levels at R + 13. Similar changes in IEG expression were also observed in the nucleus of the solitary tract, the area postrema and the central nucleus of the amygdala. In particular, in these vegetative areas the number of Fos-positive cells decreased in flight rats with respect to controls at FD14, i.e. after exposure to 0 g, but significantly increased at R + 1, i.e. after return to 1 g. Thus, altered gravitational fields produced molecular changes in vestibular nuclei controlling somatic functions, as well as in related medullary and basal forebrain structures regulating vegetative functions.

Adaptation, Physiological↗
PubMed2001

Fos-related antigens are involved in the transcriptional responses of locus coeruleus neurons to altered gravitational fields in rats.

Locus coeruleus (LC) neurons, which have widespread projections to the whole brain, respond to natural stimulation of macular receptors. Using immunocytochemistry we investigated whether rats exposed to altered gravitational fields showed changes in Fos and Fos-related antigen (FRA) protein levels in the LC. Fos protein is induced very rapidly and returns to basal levels within hours after stimulation, while FRAs persist for days or weeks after induction. Adult male albino rats (Fisher 344) were sacrificed at different time points during a space flight (NASA Neurolab Mission, STS-90) and the numbers of Fos- and FRA-positive cells in the LC were counted and compared to those in ground-based control rats. No significant changes in Fos protein expression were detected in the LC under different space flight conditions. In contrast, the number of FRA-positive cells increased on average to 167% of that of the controls at FD2, i.e. when gravity increased from 1 to 3 g during the launch before reaching about 0 g. FRA-labeled neurons then decreased to 46% of control values at FD14, i.e. after adaptation to 0 g, but increased again to 317% of control values at R + 1, when the animals were exposed to an increase in gravitational force from 0 to 1.5-1.8 g before reaching 1 g during landing. The number of labeled cells was 193% of the control values at R + 13, i.e. after readaptation to 1 g. Thus gravitational force appears to be very effective in inducing a long-term increase in FRA protein expression in the LC. Because activity in the noradrenergic LC neurons may increase Fos expression in several target structures, we postulate that the long-lasting induction of FRAs in the LC at FD2, and more prominently at R + 1, may contribute to the long-term molecular changes which probably occur in the brain during adaptation to 0 g and readaptation to 1 g.

Adaptation, Physiological↗
PubMed1994

Depression of the vestibulospinal reflex adaptation by intravermal microinjection of GABA-A and GABA-B agonists in the cat.

In decerebrate cats the gain of the vestibulospinal reflex (VSR), elicited by sinusoidal roll tilt of the animal at 0.15 Hz, +/- 10 degrees, was tested every 10-15 min during and after a sustained (3 h) period of roll tilt of the head at the parameters indicated above, associated with synchronous roll tilt of the body at 0.15 Hz, +/- 12.5 degrees; this stimulus led to 2.5 degrees of neck rotation, which was thus out of phase with respect to head rotation. In this condition the gain of the VSR progressively increased during the first h of neck-vestibular stimulation, to reach a plateau level at the end of the third h of stimulation. This adaptive process was followed for at least 1 h after stimulation. Microinjection into the zone B of the cerebellar anterior vermis of the GABA-A agonist muscimol (0.25 microliter at 8 micrograms/microliter saline) producing only a slight or negligible depression of the VSR gain in non-adaptive conditions, prevented the occurrence of the adapted increase in gain of the VSR following a 3-h period of sustained head and neck rotation. In addition, intravermal injection of the GABA-A or the GABA-B agonist muscimol or baclofen, respectively, at the same dose indicated above supressed the adapted increase in gain occurring after a 3-h period of continuous neck-vestibular stimulation. The effective sites were located into the zone B of the cerebellar anterior vermis, from which the direct corticocerebellar projection to the lateral vestibular nucleus originates. In conclusion, the results seem to indicate that the adaptive increase in gain of the VSR which occurs in decerebrate cats depend upon plastic changes which affect the Purkinje cells of the cerebellar anterior vermis. These changes were in fact suppressed by GABAergic inhibition of these neurons. The demonstration that the effects of the GABA agonists occurred suddenly makes unlikely the hypothesis that the cerebellar anterior vermis represents either a relay for adaptive changes occurring before it (for instance in the inferior olive) or else the generator of error signals that elicit plasticity in target structures (as in the vestibular nuclei).

Adaptation, Physiological↗
PubMed1994

Injections of beta-noradrenergic substances in the cerebellar anterior vermis of cats affect adaptation of the vestibulospinal reflex gain.

In precollicular decerebrate cats, intermittent sinusoidal roll tilt of the whole animal (at 0.15 Hz, +/- 10 degrees) produced a vestibulospinal reflex (VSR), characterized by an increased EMG activity of the forelimb extensor triceps brachii during side-down and a decreased activity during side-up tilt. This reflex was first tested during and after a 3-h period of sustained animal tilt at the same parameters indicated above. An adaptive increase in gain of the VSR progressively developed in some experiments, but not in others. In a second group of experiments, however, sinusoidal roll tilt of the head (0.15 Hz, +/- 10 degrees) was associated with a synchronous roll tilt of the body (at 0.15 Hz, +/- 12.5 degrees). This additional stimulus led to 2.5 degrees of neck rotation, which was thus out of phase with respect to head rotation. In all these experiments, submitted to a 3-h period of sustained neck-vestibular stimulation, the gain of the VSR tested every 10-15 min consistently increased to reach the maximum at the end of the third hour of stimulation. This adaptive process was followed up to 1 h after stimulation. Microinjection into the hemivermal cortex of the cerebellar anterior lobe of the beta-noradrenergic antagonists propranolol or sotalol (0.25-0.50 microliter at 8 micrograms/microliter saline) produced only slight and short-lasting changes in the basic amplitude of the VSR, but always decreased or prevented the occurrence of the adaptive increase in gain of the VSR during sustained out of phase head-neck rotation. The same agents also suppressed the increase in gain of the VSR which occurred in some experiments during sustained roll tilt of the whole animal (at 0.15 Hz, +/- 10 degrees), leading to selective stimulation of labyrinth receptors. On the other hand, the beta-noradrenergic agonist isoproterenol (0.25 microliters at 8 micrograms/microliters saline) brought to the light the adaptive process in other experiments in which no adaptation occurred during sustained animal rotation. These effects occurred when the sites of injection were located within the zone B of the cerebellar anterior vermis, which projects to the lateral vestibular nucleus. In conclusion, the results indicate that the adaptive changes affecting the gain of the VSR in decerebrate cats are facilitated by the noradrenergic afferent system acting on the cerebellar vermis through beta-adrenoceptors.

Adaptation, Physiological↗
PubMed1993

Adaptive modification of the cat's vestibulospinal reflex during sustained vestibular and neck stimulation.

In decerebrate cats, rotation about the longitudinal axis of the whole animal at 0.15 Hz, +/- 10 degrees produced an increased electromyogram (EMG) activity of the triceps brachii during side-down tilt and a decreased activity during side-up tilt. This vestibulospinal reflex (VSR) was tested before, during and after a sustained (3-h) period of roll tilt of the head at the parameters indicated above, associated with a synchronous roll tilt of the body at 0.15 Hz, but at the peak amplitude of either 12.5 degrees or 7.5 degrees. This additional stimulus led to 2.5 degrees of neck rotation, which was respectively out of phase (condition A) or in-phase (condition B) with head rotation. In a few instances the peak amplitude of neck rotation was increased to 5 degrees. In the first experimental condition A, the gain of the VSR (tested every 10-15 min) progressively increased, starting from the first hour of out of phase neck-vestibular stimulation to reach, on average, 241% of the control value at the end of the third hour of stimulation. On the other hand, in the second experimental condition B, the mean gain of the VSR first decreased to 82% during the first hour of in-phase neck-vestibular stimulation, but then increased to 165% of the corresponding control during the last hour of recording. In other experiments an adaptive increase in gain of the pure VSR occurred during a sustained (3-h) period of selective roll tilt of the whole animal, but it was less consistent and, on average, smaller in amplitude than that obtained during out of phase neck-vestibular stimulation. The adaptive changes in gain of the VSR described above were not associated with changes in the phase angle of the responses, and were also observed during the post-adaptation period. Further experiments indicated that the gain of the N-VSR, i.e. of the EMG responses to combined neck-vestibular stimulation, displayed a prominent adaptive increase during the sustained out of phase stimulation, but not during the in phase stimulation.

Adaptation, Physiological↗
PubMed1992

Microinjections of vasopressin in the locus coeruleus complex affect posture and vestibulospinal reflexes in decerebrate cats.

Vasopressin (VP) acts as a neurotransmitter or a neuromodulator on noradrenergic locus coeruleus (LC) neurons by exciting them. Experiments were performed in precollicular decerebrate cats to investigate whether direct infusion of VP into the LC complex of one side produced changes in posture as well as in the gain of vestibulospinal reflexes acting on forelimb extensors. Unilateral microinjection of 0.25 microliters VP solution (10(-11) micrograms/microliters saline) into the LC complex increased the extensor rigidity in the ipsilateral limbs, while that of the contralateral limbs either remained unmodified or slightly decreased. The amplitude of modulation and thus the response gain of both the ipsilateral and the contralateral triceps brachii to roll tilt of the animal leading to stimulation of labyrinth receptors decreased (t-test, P less than 0.001 for both the ipsilateral and the contralateral responses). Moreover, a slight decrease in phase lead of the responses was observed. These findings occurred 5-10 min after the injection, were fully developed within 30 min and disappeared in about 2 h. The changes in posture as well as in the gain of vestibulospinal reflexes described above were site specific and depended upon the injected neuropeptide. They were attributed to tonic activation of presumptive noradrenergic neurons, which exert a facilitatory influence on limb extensor motoneurons either directly, by utilizing the coeruleospinal pathway, or indirectly by inhibiting the dorsal pontine reticular formation and the related medullary inhibitory reticulospinal neurons.

Animals↗
PubMed1991

Locus coeruleus and dorsal pontine reticular influences on the gain of vestibulospinal reflexes.

Experimental anatomical and physiological studies have shown that noradrenergic locus coeruleus (LC) neurons, which are NE-sensitive due to inhibitory adrenoceptors, send inhibitory afferents to neurons of the peri-LC alpha and the adjacent dorsal pontine reticular formation (pRF); on the other hand these tegmental neurons, which are, in part at least, cholinergic as well as cholinoceptive, send excitatory afferents to the medullary inhibitory reticulospinal (RS) system. Experiments performed in precollicular decerebrate cats indicate that these pontine structures exert a regulatory influence on posture as well as on the gain of vestibulospinal (VS) reflexes. In particular, the increased discharge of dorsal pontine reticular neurons, and the related inhibitory RS neurons induced by microinjection of cholinergic agonists into the peri-LC alpha and the adjacent pRF of one side, decreased the postural activity, but greatly increased the response gain of the ipsilateral triceps brachii in response to stimulation of labyrinth receptors resulting from roll tilt of the animal (at 0.15 Hz, +/- 10 degrees). Similar results were also obtained when the discharge of these pontine and medullary reticular neurons was raised, either by local injection into the peri-LC alpha and the dorsal pRF of the beta-adrenergic antagonist propranolol, which blocked the inhibitory influence of the noradrenergic LC neurons on these structures, or by local injection into the LC complex of an alpha 2- or beta-adrenergic agonist (clonidine or isoproterenol) which led to functional inactivation of the noradrenergic neurons; in the latter case the effects were bilateral. Just the opposite results were obtained after microinjection into the LC of a cholinergic agonist, leading to activation of the corresponding neurons. Evidence was also presented indicating that the cholinergic excitatory afferents to the LC originated from the ipsilateral dorsal pRF. The effects described above were dose-dependent and site-specific, as shown by histological controls. Under given conditions, the decrease in postural activity induced either by direct activation of presumptive cholinergic and cholinoceptive pRF neurons or by inactivation of noradrenergic and NE-sensitive LC neurons was followed by transient episodes of postural atonia which lasted several minutes and affected the ipsilateral and sometimes also the contralateral limbs. In these instances, the EMG modulation of the corresponding triceps brachii to animal tilt was suppressed. These findings suggest two different ranges of operation for the noradrenergic and cholinergic structures located in the dorsolateral pontine tegmentum, leading either to a decrease or to an increase in gain of the VS reflexes. The cellular basis of these gain changes is discussed.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1991

Noradrenergic agents into the cerebellar anterior vermis modify the gain of vestibulospinal reflexes in the cat.

The noradrenergic (NA) afferent projection to the cerebellar cortex, which originates mainly from the locus coeruleus (LC), may act on the target neurons by utilizing both alpha- and beta-adrenoceptors. Experiments performed in decerebrate cats have shown that unilateral injection into the vermal cortex of the cerebellar anterior lobe of 0.25 microliter of the alpha 1-adrenergic agonist metoxamine or the alpha 2-agonist clonidine (at 2-8 micrograms/microliters of saline) as well as of the non-selective beta-agonist isoproterenol (at 8-16 micrograms/microliters) decreased the postural activity in the ipsilateral forelimb, while the extensor tonus either remained unmodified or slightly increased on the contralateral side. The same agents also increased the gain of the vestibulospinal (VS) reflexes elicited by recording the multiunit EMG responses of the ipsilateral and the contralateral triceps brachii to roll tilt of the animal (at 0.15 Hz, +/- 10 degrees), leading to sinusoidal stimulation of labyrinth receptors. The crossed effects were more prominent for the alpha 2- than for the alpha 1- and beta-agonists. Only slight changes in the phase angle of the responses were observed. The effects described above appeared 5-10 min after the injection, reached the peak values after 15-30 min and disappeared within 2 h. The effective area was located within the third and/or the fourth folium of the culmen rostral to the fissura prima, 1.4-1.8 mm lateral to the midline. This area corresponded to zone B of the cerebellar cortex, which projects to the ipsilateral lateral vestibular nucleus (LVN), on which it exerts a prominent inhibitory influence. In fact, monopolar stimulation of this area with three negative pulses (at 300/sec) performed prior to the local injection inhibited the spontaneous EMG activity of the ipsilateral triceps brachii. The effects described above were dose-dependent; injection of an equal volume of saline was ineffective. All changes in posture and reflexes elicited by metoxamine or clonidine were impaired by previous injection into the same corticocerebellar area of the corresponding alpha 1- or alpha 2-adrenergic antagonist prazosin or yohimbine, respectively (0.25 microliters at 8-16 micrograms/microliters). However, cross-interactions between alpha 1- and alpha 2-adrenergic agonists and antagonists were also observed. In fact, injection of the alpha 2-adrenergic antagonist yohimbine prevented the occurrence of all the metoxamine effects, while administration of the alpha 1-adrenergic antagonist prazosin prevented the occurrence of the ipsilateral, but not of the contralateral effects induced by clonidine injection.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1991

Changes in gain of vestibulospinal reflexes after local injection of beta-adrenergic substances in the cerebellar vermis of decerebrate cats.

Experiments were performed in decerebrate cats to find out whether the noradrenergic afferent system to the cerebellar cortex modified the gain of the vestibulospinal (VS) reflexes and, if so, whether this effect was mediated through beta-adrenoceptors. Unilateral injection into the vermal cortex of the culmen of the beta-adrenergic agonist isoproterenol (0.25-0.50 microliter at 8-16 micrograms/microliters of saline) increased the gain of the ipsilateral and to a lesser extent also of the contralateral triceps brachii to roll tilt of the animal at 0.15 Hz, +/- 10 degrees. The opposite result was obtained after local injection of an equal dose of the beta-adrenergic antagonist, propranolol. Only slight changes in the phase angle of the responses were obtained. The effective sites were located within the parasagittal zone B which upon stimulation inhibited the activity of the ipsilateral triceps brachii. Since most of the Purkinje (P)-cells of this corticocerebellar area, which project to the lateral vestibular nucleus, fire out-of-phase with respect to the related VS neurons, we postulate that the beta-adrenergic system enhances the amplitude of the P-cell responses to labyrinth stimulation, thus increasing the gain of the VS reflex.

Adrenergic beta-Agonists↗
PubMed1990

Responses of locus coeruleus and subcoeruleus neurons to sinusoidal stimulation of labyrinth receptors.

In precollicular decerebrate cats the electrical activity of 141 individual neurons located in the locus coeruleus-complex, i.e. in the dorsal (n = 41) and ventral parts (n = 67) as well as in the locus subcoeruleus (n = 33), was recorded during sinusoidal tilt about the longitudinal axis of the whole animal, leading to stimulation of labyrinth receptors. Some of these neurons showed physiological characteristics attributed to the norepinephrine-containing locus coeruleus neurons, namely, (i) a slow and regular resting discharge, and (ii) a typical biphasic response to fore- and hindpaw compression consisting of short impulse bursts followed by a silent period, which has been attributed to recurrent and/or lateral inhibition of the norepinephrine-containing neurons. Furthermore, 16 out of the 141 neurons were activated antidromically by stimulation of the spinal cord at T12 and L1, thus being considered coeruleospinal or subcoeruleospinal neurons. A large number of tested neurons (80 out of 141, i.e. 56.7%) responded to animal rotation at the standard frequency of 0.15 Hz and at the peak amplitude of 10 degrees. However, the proportion of responsive neurons was higher in the locus subcoeruleus (72.7%) and the dorsal locus coeruleus (61.0%) than in the ventral locus coeruleus (46.3%). A periodic modulation of firing rate of the units was observed during the sinusoidal stimulus. In particular, 45 out of the 80 units (i.e. 56.2%) were excited during side-up and depressed during side-down tilt (beta-responses), whereas 20 of 80 units (i.e. 25.0%) showed the opposite behavior (alpha-responses). In both instances, the response peak occurred with an average phase lead of about + 18 degrees, with respect to the extreme side-up or side-down position of the animal; however, the response gain (imp./s per deg) was, on average, more than two-fold higher in the former than in the latter group. The remaining 15 units (i.e. 18.7%) showed a prominent phase shift of this response peak with respect to animal position. Similar results were obtained from the subpopulation of locus coeruleus-complex neurons which fired at a low rate (less than 5.0 imp./s), as well as for the antidromically identified coeruleospinal neurons. The response gain of locus coeruleus-complex neurons, including the coeruleospinal neurons, did not change when the peak amplitude of tilt was increased from 5 degrees to 20 degrees at the fixed frequency of 0.15 Hz. This indicates that the system was relatively linear with respect to the amplitude of displacement.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Convergence and interaction of neck and macular vestibular inputs on locus coeruleus and subcoeruleus neurons.

Extracellular recordings were obtained in precollicular decerebrate cats from 90 neurons located in the noradrenergic area of the dorsal pontine tegmentum, namely in the dorsal (LCd, n = 24) and the ventral part (LC alpha, n = 40) of the locus coeruleus (LC) as well as in the locus subcoeruleus (SC, n = 26). Among these units of the LC complex, 13 were coerulospinal (CS) neurons antidromically identified following stimulation of the spinal cord at T12-L1. Some of these neurons showed the main physiological characteristics of the norepinephrine (NE)-containing LC neurons, i.e., a slow and regular resting discharge and a typical biphasic response to fore- and hindpaw compression consisting of a short burst of excitation followed by a period of quiescence, due, in part at least, to recurrent and/or lateral inhibition. Unit firing rate was analyzed under separate stimulation of macular vestibular, neck, or combined receptors by using sinusoidal rotation about the longitudinal axis at 0.15 Hz, +/- 10 degrees peak amplitude. Among the 90 LC-complex neurons, 60 (66.7%) responded with a periodic modulation of their firing rate to roll tilt of the animal and 67 (74.4%) responded to neck rotation. Convergence of macular and neck inputs was found in 52/90 (57.8%) LC-complex neurons; in these units, the gain and the sensitivity of the first harmonic of the response corresponded on the average to 0.34 +/- 0.45, SD, impulses.s-1.deg-1 and 3.55 +/- 2.82, SD, %/deg for the neck responses and to 0.23 +/- 0.29, SD, impulses.s-1.deg-1 and 3.13 +/- 3.04, SD, %/deg for the macular responses. In addition to these convergent units, 8/90 (8.9%) and 15/90 (16.7%) LC-complex units responded to selective stimulation either of macular or of neck receptors only. These units displayed a significantly lower response gain and sensitivity to animal tilt and neck rotation with respect to those obtained from convergent units. Most of the convergent LC-complex units were maximally excited by the direction of stimulus orientation, the first harmonic of responses showing an average phase lead of about +31.0 degrees with respect to neck position and +17.6 degrees with respect to animal position. Two populations of convergent neurons were observed. The first group of units (43/52, i.e., 82.7%) showed reciprocal ("out of phase") responses to the two inputs; moreover, most of these units were excited during side-down neck rotation, but inhibited during side-down animal tilt.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Responses of locus coeruleus and subcoeruleus neurons to sinusoidal neck rotation in decerebrate cat.

The electrical activity of 99 neurons located in the locus coeruleus-complex, namely in the dorsal (n = 26) and the ventral part of the locus coeruleus (n = 46) as well as the locus subcoeruleus (n = 27), has been recorded in precollicular decerebrate cats during sinusoidal displacement of the neck. This was achieved by rotation of the body about the longitudinal axis of the animal, while maintaining the head stationary. A proportion of these neurons showed some of the main physiological characteristics attributed to the noradrenergic locus coeruleus neurons, i.e. (i) a slow and regular resting discharge, and (ii) a typical biphasic response to fore and hindpaw compression consisting of short bursts of impulses followed by a period of quiescence, due at least in part to recurrent or lateral inhibition of the corresponding neurons. Moreover, 14 out of the 99 neurons were activated antidromically by stimulation of the spinal cord at T12 and L1, thus being considered as coeruleo- or subcoeruleospinal neurons. Among these locus coeruleus-complex neurons tested, 73 out of 99 (i.e. 73.7%) responded to neck rotation at the standard frequency of 0.15 Hz and at the peak amplitude of displacement of 10 degrees. In particular 40 of 73 units (i.e. 54.8%) were excited during side-down neck rotation and depressed during side-up rotation, while 18 of 73 units (i.e. 24.7%) showed the opposite pattern. In both instances the peak of the responses occurred with an average phase lead of +34.2 degrees for the extreme side-down or side-up neck displacement; however, the response gain (impulses/s per deg) was on the average more than two-fold higher in the former than in the latter group of units. The remaining 15 units (i.e. 20.5%) showed phase angle values which were intermediate between those of the two main populations. As to the coeruleo or subcoeruleospinal neurons, 11 of 14 units (78.6%) responded to the neck input, the majority (nine of 11 units, i.e. 81.8%) being excited during side-down neck rotation. Within the explored region, the proportion of responsive units was higher in the locus subcoeruleus (85.2%) than in the locus coeruleus, both dorsal and ventral (69.4%). Moreover, units located in the former structure showed on the average a response gain higher than that found in the latter structures. Similar results were also obtained from the population of locus subcoeruleus-complex neurons which fired at a low rate (less than or equal to 5.0 impulses/s).(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1989

Responses of locus coeruleus neurons to convergent neck and vestibular inputs.

The locus coeruleus (LC) complex, located in the dorsolateral pontine tegmentum, is composed of noradrenergic and self-inhibitory adrenoceptive neurons, which project to broad regions of the brain, including the spinal cord. Experiments were performed in decerebrate cats to find out whether units which had the physiological characteristics of noradrenergic neurons (i.e., a slow and regular resting discharge and a typical response to a noxious stimulus consisting of a short burst of excitation followed by a silent period), received a convergent input from both labyrinth and neck receptors. Among 90 LC-complex units, 13 of which could be identified antidromically as coeruleospinal (CS) neurons following electrical stimulation of the spinal cord at T12-L1, 52 (57.8%) responded to roll tilt of the animal and neck rotation at 0.15 Hz, +/- 10 degrees. The responses were particularly related to the extreme animal and neck displacements. Most of these convergent neurons (43/52, i.e., 82.7%) showed reciprocal ('out of phase') responses to the two inputs, while only a few units (9/52, i.e., 17.3%) showed parallel ('in phase') responses. Moreover, the majority of the 'out of phase' units showed an increased discharge during side-up animal tilt and side-down neck rotation. These predominant response patterns were just opposite to those of the vestibulospinal (VS) neurons projecting to the same segments of the spinal cord. The response characteristics of the LC-complex neurons to combined neck and vestibular inputs elicited during head rotation usually corresponded to those predicted by a vectorial summation of the individual neck and labyrinth responses, as shown for the VS neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1988

Cholinergic brainstem sites for gain control of vestibulospinal reflexes in cats.

Decerebrate cats were injected with carbachol into the locus coeruleus (LC) or with carbachol or bethanechol into the dorsal pontine reticular formation (pRF) of one side; recordings were made of the tonic contraction of forelimb extensor muscles of both sides and of their responses to sinusoidal roll tilt of the animal. Both drugs had similar effects when injected into the pRF: a decrease in the tonic contraction of limb extensors and a greatly enhanced amplitude and gain with slightly decreased phase lead in the responses to animal tilt of the forelimb extensor, triceps brachii, ipsilateral to the side of injection. Injected into the LC, carbachol produced a response opposite to the above: it increased the tonic contraction of limb extensors ipsilateral to the side of injection, but decreased the amplitude and gain of the EMG responses of limb extensor muscles to labyrinth stimulation induced by sinusoidal tilt. These findings did not depend on changes in posture since they were still observed when postural EMG activity was maintained constant by appropriate changes in static stretch of the muscle. Moreover, the magnitude of the effects increased in a dose-dependent manner. Results suggest that cholinergic activation of dorsal pRF neurons through muscarinic receptors increases the background discharge of medullary inhibitory reticulospinal (RS) system neurons, thus increasing their modulatory influence. Further, it is postulated that cholinergic activation of LC neurons would cause them to inhibit this tonic facilitatory drive by the pRF. Common to both sites of carbachol injection is the increase in phase lag of the EMG response of limb extensors to animal tilt.(ABSTRACT TRUNCATED AT 250 WORDS)

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