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O Pompeiano

Publications and source records attributed to O Pompeiano.

At least 19 recordsLinked to original sources
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↗
PubMed2002

Pineal gland hormone and idiopathic scoliosis: possible effect of melatonin on sleep-related postural mechanisms.

Experimental and clinical evidences indicate that endocrine mechanisms, particularly involving the pineal gland, exert a role in the development of postural deficits leading to the occurrence of idiopatic scoliosis (IS). In particular, experiments performed in bipedal animals have shown that removal of the pineal gland, which secretes melatonin (M), induced a scoliosis, and that in such preparations, administration of this hormone prevented the development of this deformity (cf. 131). It appears also that adolescents with IS showed a reduced level of serum M with respect to age-related control subjects. The possible mechanisms involved in the M regulation of the tonic contraction of the axial musculature have been discussed. It is known that the pineal gland is implicated in the control of circadian rhythms, including the sleep-waking cycle, and that during this cycle there are prominent changes in postural activity, which affect not only the limbs, but also the axial musculature. These changes are characterized by a decrease followed by a suppression of postural activity, which occur particularly during transition from wakefulness to synchronized sleep and, more prominently, to rapid eye movement (REM) sleep. Episodes of postural atonia may also occur during the cataplectic episodes, which are typical of narcolepsy. Cholinergic and/or cholinoceptive neurons located in the dorsal pontine reticular formation (pRF) and the related medullary inhibitory reticulospinal (RS) system, intervene in the suppression of posture during REM sleep, as well as during the cataplectic episodes which occur in narcolepsy. These structures are under the modulatory (inhibitory) influence of the dorsomedial and the dorsolateral pontine tegmentum, where serotoninergic raphe nuclei (RN) neurons and noradrenergic locus coeruleus (LC) neurons are located. We postulated that M may act not only on the circadian pacemaker, but also directly on the pontine tegmental structures involved in the regulation of posture during the animal states indicated above. This hypothesis is supported by the facts that: 1) the dorsal pRF may contain specific binding sites for M; 2) this structure is particularly sensitive to M in adolescents, as well as in adult subjects affected by narcoleptic disturbances leading to cataplexy; 3) M increases the release of serotonin (5-HT), a neurotransmitter which enhances the postural tone by acting on the dorsal pRF: on the other hand, deficits in M levels may lower the activity of the serotoninergic raphe system, thus leading to a decrease or suppression of postural activity similar to that occurring either during REM sleep or during the cataplectic episodes typical of narcoleptic patients; 4) IS patients may show episodes of sleep apnea, a phenomenon which has been attibuted to a reduced tonic contraction of primary and accessory respiratory muscles during REM, resulting from a reduced release of 5-HT at dorsal pontine level. It has been postulated that, if the reduced M and 5-HT levels are subliminal to produce a complete suppression of posture under the conditions reported above, the reduced postural tone, which results from this condition may lead to the development of IS, due to hypotonia which affects the axial musculature. M secretion could be regulated not only by the activity of the serotoninergic raphe neurons projecting to the pineal gland, but probably also by the activity of noradrenergic LC neurons. It is likely that the development of IS, which results from a reduced level of M and 5-HT, may occur provided that the noradrenergic LC inhibition of the pontine structures is impaired. Such impairment could depend upon genetic factors, similar to those postulated to play a role in narcolepsy. In conclusion, the possibility exists that an impaired activity of brain monoaminergic systems may lead to disfunction in the production of M, which is apparently an important factor in the etiopathogenesis of IS.

Animals↗
PubMed2001

Postural responses of forelimb extensors to somatosensory signals elicited during wrist rotation: interaction with vestibular reflexes.

The responses of the forelimb extensor triceps brachii (TB) to sinusoidal wrist rotation, at 0.156 Hz, +/-5 degrees, were investigated in decerebrate cats. In most of the tested muscles [12/15) the multiunit electromyographic (EMG) activity of the TB muscle increased during dorsiflexion and decreased during plantar flexion of the ipsilateral limb extremity, showing an average (+/-SD) gain of 1.38+/-0.64 impulses/s/ degrees and a phase lead of 33+/-19 degrees with respect to the extreme dorsiflexion of the forepaw. Both parameters remained unmodified by increasing the amplitude of stimulation from 5 degrees up to 10 degrees. Rotation of the contralateral wrist had no effect on TB activity. When the rotation of the ipsilateral wrist occurred during sinusoidal roll tilt of the whole animal, a stimulus that activates vestibular receptors, the TB response to combined stimulation closely corresponded to the vectorial sum of the individual responses. Dorsiflexion of the forepaw could drive the vestibulospinal system, which excites the ipsilateral TB motoneurons. In fact, functional inactivation of the cerebellar anterior vermis, which controls vestibulospinal neurons, significantly modified the TB response to wrist rotation. It appears, therefore, that the somatosensory signals elicited by wrist rotation utilize the spinocerebellum to modulate the activity of the TB. The TB responses to wrist rotation could play a role in stabilizing posture during stance and locomotion.

Animals↗
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↗
PubMed2000

Contribution of the cerebellar anterior vermis to the gain and spatiotemporal properties of the vestibulospinal reflex: a behavioural and cellular analysis.

Functional inactivation of the lobules IV-V of the cerebellar vermis obtained by local microinjection of the GABA-A agonist muscimol, depresses, in decerebrate cats, the amplitude of the VS reflex recorded from the forelimb extensor TB and may occasionally affect its spatial and/or temporal properties. The activity changes induced by tilting the animal head in all the possible directions were uniformely reduced. Experiments of unit recording from the same region submitted in other experiments to the drug injection, revealed that a large proportion of P-cells (67%) showed spatially tuned responses to the labyrinth input, characterized by preferred directions which were uniformely scattered over the horizontal plane. Neurons with opposite orientations could be found within a relatively narrow volume of corticocerebellar tissue, that could have been easily inactivated by injected volumes (0.25 microliter, 8 micrograms/microliter) of muscimol. We proposed that the spatial tuning of the P-cell responses to the labyrinth input is a basic property which allows the cerebellum to control the gain of VS reflexes elicited by head tilts in a broad directional range.

Animals↗
PubMed2000

Effects of unilateral labyrinthectomy on the norepinephrine content in forebrain and cerebellar structures of albino rats.

Albino (Wistar) rats were used to investigate whether unilateral labyrinthectomy (UL) modified the concentration of norepinephrine (NE) as well as of dopamine (DA) and the corresponding metabolite 3, 4-dihydroxyphenylacetic acid (DOPAC) in different areas of the cerebral and the cerebellar cortex and the striatum. The results obtained in 38 rats submitted to UL were compared to those of 18 rats submitted to sham-operation. The animals were operated under sodium pentobarbital anesthesia and sacrificed 1.5, 3 and 6 h after surgery. All rats submitted to UL showed phenomena of deficit (1.5-3 h after the lesion) followed by partial vestibular compensation (3-6 h after the lesion). Significant changes in the content of NE were neither found in different areas of the cerebral and the cerebellar cortex, nor in the striatum of rats sacrificed 1.5 h after UL. Three h after the lesion a bilateral increase in the NE content occurred in all the explored areas of the cerebral cortex (i.e., frontal, parieto-temporal and occipital) and the cerebellar cortex (i.e., the vermis and flocculus), as well as in the striatum. This increase, however, was more prominent in the parieto-temporal areas of the neocortex of the intact side, in all the explored areas of the cerebellar cortex of that side, as well as in the striatum of the lesioned side. This asymmetric increase in NE content could not be attributed, at least exclusively, to a generalized activation of the noradrenergic LC nuclei of both sides, due to waking and/or stress which may occur after UL, but did rather depend on asymmetric changes in unit discharge of the vestibular nuclei projecting to the LC of both sides, following UL. In particular, the increased discharge of the vestibular nuclei of the intact side would lead to activation of noradrenergic neurons projecting particularly to the parieto-temporal cortex and the cerebellar cortex of the intact side, as well as to the striatum of the lesioned side. A bilateral increase in NE content was still observed in different areas of the cerebral and cerebellar cortex of rats sacrificed 6 h after UL. This increase, however, was of smaller entity than that observed in the same areas 3 h after UL and quite symmetric. The content of DA and its metabolite DOPAC decreased bilaterally in the striatum of rats sacrificed 1.5 h after UL. This effect was attributed to a reduced synthesis and release of DA, which probably resulted from a reduced facilitatory influence that the deafferented vestibular nuclei exert on the dopaminergic, nigrostriatal system of both sides, although mainly on the intact side. The corresponding values, however, bilaterally recovered to slightly increase with respect to the control values in rats sacrificed 3 and 6 h after UL. In these experiments the content of both DA and DOPAC remained symmetric on both sides after UL, in contrast with the bilateral but asymmetric increase in NE concentration observed in the same structure 3 h the lesion. The present results integrate and extend those of previous experiments showing that: 1) albino rats sacrificed 6 h after UL displayed an increased synthesis of NE, which affected particularly the LC of the intact side as well as the medial vestibular nuclei of both sides (21); and 2) the structures which showed an increased content of NE at given time intervals after UL also displayed an increase in the expression of the immediate early gene c-fos (cf. 16 for ref.). These findings suggest that bilateral but asymmetric activation of the noradrenergic LC neurons following UL may lead to an asymmetric increase in c-fos expression in several target structures, thus contributing to the plastic changes responsible for vestibular compensation. In conclusion, it appears that UL induces in several brain structures of albino rats a short-term increase in synthesis and release of NE. (ABSTRACT TRUNCATED)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1999

Neck input modifies the reference frame for coding labyrinthine signals in the cerebellar vermis: a cellular analysis.

The activity of 68 neurons, mainly Purkinje cells, was recorded from the cerebellar anterior vermis of decerebrate cats during wobble of the whole animal (at 0.156 Hz, 5 degrees), a mixture of tilt and rotation, leading to stimulation of labyrinth receptors. Most of the neurons (65/68) were affected by both clockwise and counterclockwise rotations. Twenty-four units showing responses of comparable amplitude to these stimuli (narrowly tuned cells) were represented by a single vector (Smax), whose preferred direction corresponded to the direction of stimulation giving rise to the maximal response. The remaining 41 units, however, showed different amplitude responses to these rotations (broadly tuned cells) and were characterized by two spatially and temporally orthogonal vectors (Smax and Smin), suggesting that labyrinthine signals with different spatial and temporal properties converged on these cells. All these units were tested while the body was aligned with the head (control position), as well as after static displacement of the body under a fixed head by 15 degrees and/or 30 degrees around a vertical axis passing through C1-C2, thus leading to stimulation of neck receptors. The orientation component of the response vector of the Purkinje cells to vestibular stimulation changed following body-to-head displacement. Moreover, the amplitude of vector rotation corresponded, on the average, to that of body rotation. Changes in temporal phase, gain and tuning ratio of the responses were also observed. We propose that information from neck receptors regulates the convergence of labyrinthine signals with different spatial and temporal properties on corticocerebellar units. Due to their strict relationship with the motor system, these units may give rise to appropriate responses in the limb musculature, by modifying the spatial organization of the vestibulospinal reflexes according to the requirements of body stability. The cerebellar vermis may thus represent an important structure, where frames of reference can be altered to account for changes in position of trunk, head and neck.

Animals↗
PubMed1999

Effects of locus coeruleus stimulation on the responses of SI neurons of the rat to controlled natural and electrical stimulation of the skin.

1. The effects of microstimulation of the locus coeruleus (LC) region on the spontaneous discharge and the response of SI neurons to natural and electrical stimulation of the skin have been investigated in 26 urethane anesthetized Sprague-Dawley rats. In particular, one or two air puffs, 5-10 msec in duration, 1-2 psi, usually separated by an interval of 40 msec, were applied on the hairy skin of the wrist or the forepaw at the presentation rate of 1/sec. For units unresponsive to air puffs, similar presentation of low intensity electrical stimuli (0.2-5.0 V, 0.2-0.4 msec pulses) were applied through two needles inserted on the most effective area of the skin. Both natural and electrical stimulations of the skin were applied under control conditions, as well as 50 msec after a 250 msec train of 0.3 msec pulses at 40 Hz. 20-30 microA applied stereotaxically to the LC complex through a tungsten microelectrode. 2. Not all cortical units exhibited spontaneous discharge. Most of the units, however, which were spontaneously active, were inhibited by electrical stimulation of the LC complex, while the remaining ones were excited. The sites of stimulation, which included either the LC proper or the locus subcoeruleus, were identified following both anatomical and physiological criteria. 3. SI neurons recorded at sites between 400 and 950 microns below the surface of the cortex, thus being most likely granule cells of layers III and IV, responded to cutaneous stimuli with spikes which occurred with a latency of 20-30 msec in response to single air puffs and a latency of 15-20 msec in response to single electrical pulses to the skin. In both instances the response to the second stimulus applied at the interstimulus interval of 40 msec was markedly reduced or abolished due to postexcitatory inhibition following the response to the first stimulus (in-field inhibition). In contrast, units particularly located at or below 1000 microns from the cortical surface, which were of very large size probably corresponding to large layer V pyramidal cells, were often difficult to activate with air puffs applied at the centre of the receptive field (RF) and were submitted to electrical stimulation of the skin. 4. Among the 59 isolated SI units tested either to air puffs (45 neurons) or to electrical skin stimulation (14 neurons), 15 units (i.e., 25.4%) were facilitated, while 12 units (i.e., 20.3%) were inhibited following stimulation of the LC complex. 5. A marked feature of the facilitatory effects which usually involved the predominant response to the first air puff, but also the smaller response to the second puff, was that the increase in the number of spikes per stimulus was accompanied by a temporal focusing of the responses characterized by a clear tightening of the latency and narrowing of the peak of activity, which was often accompanied by some level of tonic inhibition of the background discharge. Thus, LC stimulation increased the signal-to-noise ratio of SI neuronal responses to skin stimulation. When inhibitory effects were induced by LC stimulation, they clearly affected the unit response to the first air puff, which was severely depressed. However, the response to the second puff could be facilitated, suggesting that LC stimulation might have produced inhibition of those inhibitory interneurons responsible for the postexcitatory inhibition of the units under examination. Evidence for spatial focusing of the response was not easily documented. In some units, however, LC stimulation produced either facilitation of the responses to puffs at the receptive field center and inhibition of the responses to puffs at the edge at the receptive field or vice versa. 6. Since the LC complex contains in the rat a predominant population of noradrenergic neurons, it is likely that the effects described above were mainly due to activation of these noradrenergic neurons. 7. (ABSTRACT TRUNCATED)

Animals↗
PubMed1998

Convergence of directional vestibular and neck signals on cerebellar purkinje cells.

Convergence of spatially oriented vestibular and neck signals within the cerebellar anterior vermis in decerebrate cats was studied by recording the simple spike discharge of Purkinje (P) cells during wobble either of the whole animal (vestibular input) or of the body under a fixed head (neck input) at 0.156 Hz, 5 degrees and 2.5 degrees , respectively. Both clockwise (CW) and counterclockwise (CCW) rotations were performed. Units that had equal response amplitudes to CW and CCW rotations (narrowly tuned neurons) were described by a single vector (Smax), characterized by a gain, a direction and a temporal phase. Units with different response amplitudes to CW and CCW rotation (broadly tuned neurons) were described by two vectors (Smax and Smin). In addition to these bidirectional units, there were also unidirectional units which responded either to CW or CCW rotation; in these cases the gain of Smax equals that of Smin. On the whole, 77% and 63% of the P cells responding to vestibular and neck stimulation, respectively, showed a bidirectional broadly tuned or unidirectional behavior. These response patterns were attributed to the convergence of signals with different spatial and temporal properties. About 50% of the P cells from which recordings were made responded to stimulation of both sensory systems. However, the gains of the Smax vectors of the neck responses were much greater than those of the vestibular responses, at least for small amplitudes of rotation, and were positively correlated with them. Usually the differences in the orientation components of the neck and vestibular Smax vectors were larger, while the differences in temporal phases were smaller than 90 degrees . These findings suggest that periodic changes in the phase difference and gain ratio of the neck to the vestibular response may occur during dynamic displacement of the head over the body, depending on the stimulus direction. As a result of these data, the P cells of the cerebellar vermis are expected to show prominent responses to head rotation, which could affect the spatially organized postural responses by utilizing vestibular and reticular targets.

Animals↗
PubMed1998

Vasopressin in the locus coeruleus and dorsal pontine tegmentum affects posture and vestibulospinal reflexes.

Vasopressin (VP) acts on both the locus coeruleus (LC) neurons and the neighbouring dorsal pontine reticular formation (PRF) neurons by exciting them. Experiments performed in precollicular decerebrate cats have shown that microinjection of 0.25 x 10(-11) micrograms VP into the LC complex of one side increased the extensor rigidity of the ipsilateral limbs, while rigidity of the contralateral limbs remained unmodified or slightly decreased. The amplitude of modulation and thus the response gain of both the ipsilateral and the contralateral forelimb extensor triceps brachii to sinusoidal roll tilt of the animal (at 0.15 Hz, +/- 10 degrees), leading to stimulation of labyrinth receptors, decreased significantly, while there was only a slight decrease in phase lead of the responses. These effects occurred 5-10 min after the injection, were fully developed within 30 min and disappeared in about 2 h. VP activation of presumed noradrenergic LC neurons had a facilitatory influence on ipsilateral limb extensor motoneurons, either directly through the coeruleospinal (CS) pathway, or indirectly by inhibiting the dorsal PRF and the related medullary inhibitory reticulospinal (RS) neurons. Moreover, because the facilitatory CS neurons fire out-of-phase with respect to the excitatory VS neurons, we postulated that the higher the firing rate of the CS neurons in the animal at rest, the greater the disfacilitation affecting the limb extensor motoneurons during side-down animal tilt. These motoneurons would then respond less efficiently to the excitatory VS volleys elicited for the same direction of animal orientation, leading to a reduced gain of the EMG responses of the forelimb extensors to labyrinth stimulation. In contrast to these findings, unilateral injections of the same dose of VP immediately ventral to the LC, i.e., in the peri-LC alpha and the surrounding dorsal PRF, where presumed cholinergic neurons are located, decreased extensor rigidity in the ipsilateral limbs while that of the contralateral limbs either decreased or increased. The same injection also produced either a moderate or a marked increase in gain of the multiunit EMG response of the ipsilateral triceps brachii to animal tilt. In the first instance the response gain of the contralateral triceps brachii to animal tilt increased slightly, while the corresponding response pattern remained unmodified, as shown for the ipsilateral responses (increased EMG activity during ipsilateral tilt and decreased activity during contralateral tilt). In the second instance, however, the response gain of the contralateral triceps brachii showed only slight changes, while the pattern of response was reversed. These effects occurred 5-20 min after the injection, developed fully within 20-60 min and disappeared in 2-3 h. We postulated that VP increased the discharge of the dorsal PRF neurons and the related medullary inhibitory RS neurons of the injected side, leading to reduced postural activity of the ipsilateral limbs. However, because these inhibitory RS neurons fire out-of-phase with respect to the excitatory VS neurons, it appeared that the higher the firing rate of the RS neurons in the animal at rest, the greater the disinhibition affecting the limb extensor motoneurons during ipsilateral tilt. These motoneurons would then respond more efficiently to the same excitatory VS volleys elicited by given parameters of stimulation, leading to an increased gain of the EMG responses. The contralateral effects could be attributed to crossed excitation by dorsal PRF neurons of one side, either of medullary inhibitory RS neurons or of excitatory CS neurons of the opposite side, respectively. We conclude that VP controls posture and gain of the VS reflex by acting on LC neurons as well as on dorsal PRF and the related medullary inhibitory RS neurons.

Animals↗
PubMed1998

Noradrenergic influences on the cerebellar cortex: effects on vestibular reflexes under basic and adaptive conditions.

Experiments performed either in decerebrate cats or in intact rabbits have shown that functional inactivation of the cerebellar anterior vermis or the flocculus decreased the basic gain of the vestibulospinal or the vestibulo-ocular reflex, respectively. These findings were attributed to the fact that a proportion of the vermal or floccular Purkinje cells, which are inhibitory in function, discharge out of phase with respect to the vestibulospinal or the vestibulo-ocular neurons during sinusoidal animal rotation, thus exerting a facilitatory influence on the gain of the vestibular reflexes. Intravermal injection of a beta-noradrenergic agonist slightly increased the gain of the vestibulospinal reflex, whereas the opposite result was obtained after injection of beta-antagonists. Similarly, intrafloccular injection of a beta-noradrenergic agonist slightly facilitated the gain of the vestibulo-ocular reflex in darkness (but not in light), whereas a small decrease of the reflex occurred after injection of a beta-antagonist. It was postulated that the noradrenergic system acts on Purkinje cells by enhancing their amplitude of modulation to a given labyrinth signal, thus increasing the basic gain of the vestibular reflexes. The Purkinje cells of the cerebellar anterior vermis and the flocculus also exert a prominent role on the adaptation of vestibulospinal and vestibulo-ocular reflexes, respectively. In particular, intravermal or intrafloccular injection of beta-noradrenergic antagonists decreased or suppressed the adaptive capacity of the vestibulospinal and vestibulo-ocular reflexes that always occurred during sustained out-of-phase neck-vestibular or visual-vestibular stimulation, whereas the opposite result was obtained after local injection of a beta-noradrenergic agonist. The noradrenergic innervation of the cerebellar cortex originates from the locus coeruleus complex, whose neurons respond to vestibular, neck, and visual signals. It was postulated that this structure acts through beta-adrenoceptors to increase the expression of immediate-early genes, such as c-fos and Jun-B, in the Purkinje cells during vestibular adaptation. Induction of immediate-early genes could then represent a mechanism by which impulses elicited by sustained neck-vestibular or visuovestibular stimulation are transduced into long-term biochemical changes that are required for cerebellar long-term plasticity.

Adaptation, Physiological↗
PubMed1998

Spatiotemporal response properties of cerebellar Purkinje cells to neck displacement.

The activity of 184 Purkinje cells and 58 unidentified neurons located within the cerebellar anterior vermis was recorded in decerebrate cats during wobble of the body under a fixed head. This stimulus induced a neck displacement of constant amplitude (2.5 degrees) whose direction rotated at the constant velocity of 56.2 degrees/s on the horizontal plane, both in the clockwise and counterclockwise directions. It was then possible to evaluate the spatiotemporal characteristics of unit responses to neck displacement in the vertical planes; 131 of 184 Purkinje cells (71%) and 35 of 58 unidentified cells (60%) responded to clockwise and/or counterclockwise rotations. In particular, among the responsive units, 44% of the Purkinje cells and 37% of the unidentified cells showed an equal amplitude modulation during clockwise and counterclockwise rotations. These units are expected to show a maximal response sensitivity for neck displacement in a preferred direction, a null response for perpendicularly oriented stimuli and a constant temporal phase (narrowly tuned neurons). In 28% of the Purkinje cells and 40% of the unidentified cells, responses of different amplitudes were observed during clockwise and counterclockwise rotations. These neurons should display a preferred direction of response to neck displacement, lack of null response directions and a temporal phase changing with the stimulus direction (broadly tuned neurons). Finally, 27% of the Purkinje cells and 23% of the unidentified cells responded only to wobble in the clockwise or counterclockwise direction (unidirectional units). This behavior predicts equal sensitivities for all the directions of neck displacement and a response phase changing linearly with the direction of neck displacement. A maximal sensitivity vector (Smax), aligned with the preferred direction of the neuron, was evaluated for the bidirectional narrowly tuned and broadly tuned units. Its amplitude and temporal phase corresponded to the response characteristics expected for stimuli in the preferred direction of the cell. Smax directions were distributed over the horizontal plane. Most of them, however, were closer to the pitch than to the roll axis and pointed towards the animal's tail. Among pitch-related Purkinje cells, the temporal phase of Smax was small with a predominance of phase lags; phase leads of rather large amplitude were usually observed for roll-related Purkinje cells. The possibility that the recorded population of units coded the direction of neck displacement was tested by assuming that each cell gave a vectorial contribution related to its response properties and that the vectorial sum of such contributions represented the outcome of the population code. Dynamic body-to-head displacements in four different directions were simulated and for each direction 12 population vectors were evaluated at regular intervals of the stimulus cycle. The direction of the population vector was related to that of the stimulus, but the correspondence was close only for the pitch direction. Moreover, the amplitude of the population vector depended upon the direction of the stimulus, being larger for pitch than for roll displacements. Due to the efferent connections of the explored cerebellar region, the neuronal signals generated by the Purkinje cell population are probably transferred to the spinal cord, where they may differentially affect the amplitude and the spatial properties of the neck reflexes according to the direction of neck displacement.

Animals↗
PubMed1998

Fos-protein expression in noradrenergic locus coeruleus neurons after unilateral labyrinthectomy in the rat.

c-Fos mRNA and the related Fos-protein are rapidly induced by physiological stimuli and can be used as molecular markers of neural activation and plasticity. In a recent study (14), we found that rats submitted to unilateral labyrinthectomy (UL) displayed an asymmetric increase in the expression of both c-fos and Fos-protein not only in several vestibular, precerebellar and cerebellar structures and the caudate-putamen, but also in the locus coeruleus (LC)-complex, whose neurons integrate labyrinthine signals and are apparently involved in the plastic changes which are at the basis of vestibular compensation. In the present study we investigated the putative noradrenergic nature of the Fos-positive LC neurons observed after UL by combining Fos-protein immunocytochemistry with the immunocytochemical detection of tyrosine hydroxylase (TH), a synthetizing enzyme of noradrenaline. The experiments were performed in rats sacrificed 3, 6 and 24 h after surgical lesion of one labyrinth. The results obtained were in agreement with the previous findings, showing that already 3 h after UL an asymmetric increase of the c-fos and/or Fos-protein expression occurred in the vestibular nuclei, the inferior olive, the cerebellar cortex and the caudate-putamen. Most interestingly, the Fos-protein expression markedly increased in the LC-complex of both sides, although mainly ipsilaterally to the intact side. It appeared also that several Fos-positive LC-complex neurons were probably noradrenergic in nature, as they could be double-labeled with the Fos/TH technique. These findings were attenuated 6 h after UL and disappeared after 24 h, when partial compensation of the vestibular syndrome had occurred. Thus, UL results in asymmetric functional activation in the LC region of well identified noradrenergic neurons. This finding is attributed to the fact that asymmetric stimulation of labyrinth receptors gives rise to asymmetric changes in firing rate of LC neurons (45). Since these neurons send noradrenergic afferents to several target structures such as the vestibular nuclei, the inferior olive, the cerebellar cortex and the caudate-putamen, we postulated that the asymmetric labyrinthine activation of the noradrenergic LC system, occurring after UL, could increase the Fos-protein expression in the above mentioned brain structures. This possibility could then represent a key factor in determining the plastic changes, which are at the basis of vestibular compensation.

Animals↗
PubMed1998

Cholinergic neurons of the dorsal pontine tegmentum projecting to the cerebellar vermal cortex of the kitten.

Although the whole cerebellar cortex receives cholinergic afferents, the source of origin of this projection has been clarified only for some corticocerebellar regions. Experiments were performed in kittens to investigate whether the two major cholinergic groups of the brainstem, the pedunculopontine (PPT) and laterodorsal tegmental nuclei (LDT), contribute to the cholinergic innervation of the cerebellar cortex, in particular the vermal cortex. Tegmento-cerebellar projecting neurons were identified by injecting the retrograde tracer rhodamine-labeled latex microspheres in the lobules V to VII of the cerebellar vermis. Subsequently, some of these tegmento-cerebellar neurons were demonstrated to be cholinergic by using the immunohistochemical technique for choline acetyltransferase (ChAT). Only a small portion of the ChAT-positive tegmental neurons projected to the cerebellar vermis. However, among the whole population of the retrogradely labeled tegmental neurons about one third were cholinergic. These cholinergic tegmento-cerebellar neurons were located in the PPT, LDT, and also within the locus coeruleus (LC) complex, where noradrenergic neurons predominate. Since the LC complex sends noradrenergic afferents to the cerebellar cortex, it appears that the dorsal pontine area contributes to the tegmento-cerebellar projections not only with noradrenergic but also with cholinergic afferents. The physiological significance of this cholinergic projection to the cerebellar cortex has been discussed.

Animals↗