Biomedical subjects

O Pompeiano

Publications and source records attributed to O Pompeiano.

At least 19 recordsLinked to original sources

PubMed1992

Noradrenergic and cholinergic modulations of corticocerebellar activity modify the gain of vestibulospinal reflexes.

In addition to mossy fibers and climbing fibers, the cerebellar cortex receives noradrenergic and cholinergic afferents. Since the Purkinje (P) cells of the cerebellar vermis (culmen) respond to roll tilt of the animal with a discharge pattern that is out of phase with respect to that of the related lateral vestibular neurons, thus exerting a facilitatory influence on the gain of the vestibulospinal (VS) reflex, we tested the effects of local microinjection into the anterior vermis of noradrenergic and cholinergic agents on these reflexes. In decerebrate cats, unilateral microinjection in the paramedial zone B of the culmen of 0.25 microliters of small doses of alpha 1-, alpha 2-, and beta-noradrenergic agonists (i.e., metoxamine, clonidine, and isoproterenol, respectively) increased the response gain (in impulses/second per deg) of the EMG response of the ipsilateral and to some extent also of the contralateral triceps brachii to animal tilt (at 0.15 Hz, +/- 10 degrees). On the other hand local injection of the corresponding antagonists (i.e., prazosin, yohimbine, and propranolol) either decreased the gain of the ipsilateral triceps brachii to labyrinth stimulation or else prevented the occurrence of the effects induced by the corresponding agonists. An increase in gain of the VS reflexes was also elicited in other experiments by unilateral microinjection either of the nonselective cholinergic agonist carbachol or of the anticholinesterase eserine sulfate. Thus, the effects could be produced by increasing the naturally present amount of acetylcholine. Further experiments indicated that a bilateral increase in the response gain of the triceps brachii to labyrinth stimulation occurred after microinjection of a selective muscarinic (bethanechol) or nicotinic agonist (nicotine), while just the opposite result was obtained after microinjection of the corresponding muscarinic (scopolamine) and nicotinic (hexamethonium, D-tubocurarine) blockers. The effects of the noradrenergic and cholinergic agonists, which persisted for about two hours after the injection, were site specific and dose dependent. It appears, therefore, that the noradrenergic and cholinergic afferents to the cerebellar vermis intervene in the gain regulation of the VS reflexes, possibly by increasing the amplitude of modulation of the P cells to labyrinth stimulation.

Animals↗

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↗

PubMed1992

Modulation of desynchronized sleep through microinjection of alpha 1-adrenergic agonists and antagonists in the dorsal pontine tegmentum of the cat.

Noradrenaline is involved in the regulation of the sleep/waking cycle by acting through various receptor types. In previous studies we investigated the role of beta- and alpha 2-adrenergic receptors through local microinjections of various drugs into the dorsal pontine tegmentum (DPT) of the cat. This region is known to be crucially involved in desynchronized sleep execution. In this study we examined the role of alpha 1-adrenergic receptors. The alpha 1-agonist methoxamine and the alpha 1-antagonist prazosin were injected into the DPT of freely moving, unanaesthetized cats. We found that methoxamine notably reduced desynchronized sleep, and that this effect was both dose-dependent and site-specific. These effects were prevented by the subsequent injection of prazosin. On the other hand, the injection into the DPT of prazosin alone produced scarce or inconsistent effects on the sleep/waking cycle.

Animals↗

PubMed1992

GABA receptors in Deiters nucleus modulate posturokinetic responses to cortical stimulation in the cat.

The early component of the postural responses which accompany the limb flexion during unilateral stimulation of the motor cortex in the cat is not of reflex origin, but results from a central command. These postural adjustments are characterized by a decreased force under the limb diagonally opposite to the moving one and an increased force under the other two. Since the lateral vestibular nucleus (LVN) exerts an excitatory influence on ipsilateral limb extensor motoneurons, experiments were performed in cats to establish whether the cortical-induced postural changes were mediated through the LVN. This structure is tonically inhibited by GABAergic synapses originating from Purkinje cells of the cerebellar vermis, so that local microinjection into the LVN of GABA agonists or antagonists should either decrease or increase the spontaneous discharge of their neurons. Unilateral microinjection of 0.25 microliters of the GABA-A agonist muscimol or the GABA-B agonist baclofen (at 2-4 micrograms/microliters saline) into the LVN produced a short-lasting episode of ipsilateral postural hypotonia and contralateral hypertonia, during which the cats were unable to stand on the measurement platform. When, shortly after, some recovery of the postural activity appeared, no changes in threshold, latency or amplitude of the cortical-induced flexion movement were observed; however, the early component of the postural responses decreased in the other three limbs. Moreover, the slope of the response curve of the moving limb remained unmodified, while that of the early component of the postural responses, which involved the remaining limbs, decreased following stimulation of the motor cortex at different stimulus intensities. These effects started a few min after the injection and lasted for about 2-3 h. The effects described above were dose-dependent. Moreover, histological controls indicated that the structure responsible for these postural changes corresponded to the middle part of the LVN. The specificity of the results was shown by the fact that unilateral microinjection of 0.25 microliters of the GABA-A antagonist bicuculline or the GABA-B antagonist phaclofen (at 5-8 micrograms/microliter saline) into the LVN produced a postural asymmetry opposite in sign to that elicited in the same experiments by the corresponding agonists. These injections did not modify the amplitude of the cortical-induced limb flexion, but rather enhanced the amplitude of the early component of the postural responses in the other three limbs.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1992

Muscarinic receptors in the cerebellar vermis modulate the gain of the vestibulospinal reflexes in decerebrate cats.

1. The Purkinje (P)-cells of the cerebellar vermis, which exert a prominent influence on posture as well as on the gain of vestibulospinal (VS) reflexes, are under the control not only of the classic mossy fibers and climbing fibers which liberate excitatory amino acids as neurotransmitter, but also of cholinergic afferents. The role of these afferents was investigated in precollicular decerebrate cats by using the method of local microinjection of cholinergic agents into appropriate areas of the cerebellar cortex. 2. Unilateral injection into the vermal cortex of the culmen of the non-selective cholinergic agonist carbachol (0.25 microliters at 0.5 micrograms/microliters saline) produced a postural asymmetry, characterized by a slight decrease of the extensor tonus in the ipsilateral forelimb and an increased tonus in the contralateral forelimb. Moreover, the gain of the EMG responses of the ipsilateral and the contralateral triceps brachii to animal tilt increased significantly, while no significant changes in the phase angle of the responses were observed. These effects started 5-10 min after the injection and persisted for at least 2 hours before disappearing. Similar but smaller effects were obtained after injection of eserine, an inhibitor of acetylcholinesterase. Thus, the effects could be produced by increasing the naturally present amount of acetylcholine (ACh). 3. The changes in posture and gain of the VS reflexes described above utilized in part at least muscarinic receptors, since effects similar to those induced by carbachol injection were also obtained after unilateral microinjection into the vermal cortex of the culmen of the muscarinic agonist bethanechol (0.25 microliters at 0.1 micrograms/microliters). On the other hand opposite effects, characterized by an increased postural activity in the ipsilateral forelimb associated with a decreased activity in the contralateral forelimb, as well as by a reduced gain of the EMG responses of the triceps brachii of both sides to animal tilt were observed in other experiments after local microinjection of the muscarinic antagonist scopolamine (0.25 microliter at 4-8 micrograms/microliters saline). Evidence for muscarinic supersensitivity was obtained following repetitive injections of scopolamine into the cerebellar vermis. 4. The area which upon injection of the cholinergic agents modified the postural activity as well as the gain of the VS reflexes was located within the third and/or the fourth folium rostral to the fissura prima (culmen), at the laterality of 1.4-1.8 mm with respect to the midline.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

PubMed1992

Effects of microinjection of vasopressin in dorsal pontine reticular structures on the gain of vestibulospinal reflexes in decerebrate cats.

1. The possibility that vasopressin (VP) acts on the dorsal pontine reticular formation (pRF) and the related medullary inhibitory reticulospinal (RS) system to control posture as well as the vestibulospinal reflexes has been investigated by injecting small doses of VP in precollicular decerebrate cats. 2. Unilateral microinjection of VP (0.25 microliters at the concentration of 10(-11) micrograms/microliters saline) in the pRF decreased the extensor rigidity in the ipsilateral limbs, while that of the contralateral limbs either decreased or increased. The same injection also produced a moderate or a prominent increase in gain of the multiunit EMG responses of the ipsilateral triceps brachii to roll tilt of the animal (t-test, P less than 0.001 for either group of responses). In the first instance the response gain of the contralateral triceps brachii to animal tilt slightly increased, while the pattern of response remained always of the alpha-type, 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 showed only slight changes, while the pattern of responses reversed from the alpha- to the beta-type. These findings occurred 5-20 min after the injection, fully developed within 30-60 min and disappeared in about 2-3 hours. 3. The structures responsible for the postural and reflex changes described above were located in the dorsal pontine tegmental region immediately ventral to the LC, and included the peri-LC alpha and the surrounding dorsal pRF. The induced effects depended upon the injected neuropeptide, since previous injection of an equal volume of saline stained by the pontamine sky blue dye into the same dorsal pontine area was ineffective. 4. We postulated that VP exerts an excitatory influence on ipsilateral dorsal pRF neurons. The increased discharge of these neurons and the related medullary inhibitory RS neurons would lead to a decreased postural activity in the ipsilateral limbs. However, since these inhibitory RS neurons fire out of phase with respect to the excitatory vestibulospinal neurons, it appears that the higher the firing rate of the RS neurons in the animal at rest, the greater the disinhibition that affects the limb extensor motoneurons during ipsilateral tilt. These motoneurons would then respond more efficiently to the same excitatory volleys elicited by given parameters of stimulation, thus leading to an increased gain of the EMG responses.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1991

Effects of alpha-noradrenergic substances on the optokinetic and vestibulo-ocular responses in the rabbit: a study with systemic and intrafloccular injections.

The effects of microinjection of alpha-noradrenergic agonists and antagonists in the flocculus on the basic gain and adaptibility of vestibulo-ocular and optokinetic responses were investigated. A complementary, previous investigation had shown that the adaptation, but not the basic performance, of compensatory oculomotor responses were markedly influenced by beta-noradrenergic mechanisms in the flocculus. In contrast, the present experiments with bilateral, intrafloccular injections of phenylephrine, prazosin, clonidine and idazoxan failed to reveal any effect of alpha 1- or alpha 2-noradrenergic mechanisms on either basic performance or adaptation of compensatory eye movements. Intravenous administration of clonidine, however, reduced the gain of the optokinetic and vestibulo-ocular responses by about 70 and 50%, respectively, at dosages of 0.07 mg/kg. Recovery from this effect took about 1.5 h. A higher dosage of clonidine (0.7 mg/kg) had a similar, but longer lasting effect, and also markedly increased the frequency of spontaneous saccades. Intravenous administration of phenylephrine did not affect the oculomotor responses. It is concluded that the control of oculomotor responses is not susceptible to alpha-noradrenergic influences at the level of the flocculus, but that alpha 2-agonistic action inhibits these responses through an extra-floccular structure.

Adaptation, Physiological↗

PubMed1991

Locus coeruleus control of spinal motor output.

Using electrophysiological techniques, we investigated the functional properties of the coeruleospinal system for regulating the somatomotor outflow at lumbar cord levels. Many of the fast-conducting, antidromically activated coeruleospinal units were shown to exhibit the alpha 2-receptor response common to noradrenergic locus coeruleus (LC) neurons. Electrically activating the coeruleospinal system potentiated the lumbar monosynaptic reflex and depolarized hindlimb flexor and extensor motoneurons via an alpha 1-receptor mechanism. The latter synaptically induced membrane depolarization was mimicked by norepinephrine applied iontophoretically to motoneurons. That LC inhibited Renshaw cell activity and induced a positive dorsal root potential at the lumbar cord also reinforced LC's action on motor excitation. We conclude that LC augments the somatomotor output, at least in part, via an alpha 1-adrenoceptor-mediated excitation of ventral horn motoneurons. Such process is being strengthened by LC's suppression of the recurrent inhibition pathway as well as by its presynaptic facilitation of afferent impulse transmission at the spinal cord level.

Action Potentials↗

PubMed1991

Responses of locus coeruleus neurons to labyrinth and neck stimulation.

The electrical activity of a large population of locus coeruleus (LC)-complex neurons, some of which were antidromically activated by stimulation of the spinal cord at T12-L1, was recorded in precollicular decerebrate cats during labyrinth and neck stimulation. Some of these neurons showed physiological characteristics attributed to norepinephrine (NE)-containing LC neurons, i.e., (i) a slow and regular resting discharge; (ii) a typical biphasic response to compression of the paws consisting of short impulse bursts followed by a silent period, which was attributed to recurrent and/or lateral inhibition of the corresponding neurons; and (iii) a suppression of the resting discharge during episodes of postural atonia, associated with rapid eye movements (REM), induced by systemic injection of an anticholinesterase, a finding which closely resembled that occurring in intact animals during desynchronized sleep. Among the neurons tested, 80 of 141 (i.e., 56.7%) responded to the labyrinth input elicited by sinusoidal tilt about the longitudinal axis of the whole animal at the standard parameters of 0.15 Hz, +/- 10 degrees, and 73 of 99 (i.e., 73.7%) responded to the neck input elicited by rotation of the body about the longitudinal axis at the same parameters, while maintaining the head stationary. A periodic modulation of firing rate of the units was observed during the sinusoidal stimuli. In particular, most of the LC-complex units were maximally excited during side-up tilt of the animal and side-down neck rotation, the response peak occurring with an average phase lead of about +17.9 degrees and +34.2 degrees with respect to the extreme animal and neck displacements, respectively. Similar results were also obtained from the antidromically identified coeruleospinal (CS) neurons. The degree of convergence and the modalities of interaction of vestibular and neck inputs on LC-complex neurons were also investigated. In addition to the results described above, the LC-complex neurons were also tested to changing parameters of stimulation. In particular, both static and dynamic components of single unit responses were elicited by increasing frequencies of animal tilt and neck rotation. Moreover, the relative stability of the phase angle of the responses evaluated with respect to the animal position in most of the units tested at increasing frequencies of tilt allowed the conclusion to attribute these responses to the properties of macular ultricular receptors. This conclusion is supported by the results of experiments showing that LC-complex neurons displayed steady changes in their discharge rate during static tilt of the animal.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

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

Effects of GABAergic and noradrenergic injections into the cerebellar flocculus on vestibulo-ocular reflexes in the rabbit.

The role of the vesitibulo-cerebellum of the rabbit in the control of the vestibulo-ocular response (VOR) and optokinetic response (OKR) reflexes was investigated by bilateral microinjections, into the flocculus, of substances affecting GABAergic or noradrenergic neurotransmission. GABA, the main transmitter through which cerebellar interneurons inhibit Purkinje cells directly or indirectly, acts normally through GABAA receptors (mainly located in the granular layer) and GABAB receptors (predominantly located in the molecular layer). Despite this different distribution, floccular injections of the GABAA agonist muscimol and of the GABAB agonist baclofen had a similar effect, presumably by profound inhibition of Purkinje cells. This effect consisted of a reduction in the gain of the VOR (in darkness and in light) as well as of the OKR by at least 50%. This provides firm evidence that the net effect of normal Purkinje-cell activity in the flocculus is to enhance the VOR and OKR, rather than to inhibit these responses, as is sometimes supposed. Intrafloccular injections of the beta-noradrenergic agonist isoproterenol or the beta-noradrenergic antagonist sotalol did not affect the basic magnitude of the VOR and OKR. However, these substances markedly affected the adaptive processes, which cause the VOR and OKR to change its magnitude when this is no longer adequate in stabilizing the retinal image. By a suitable combination of vestibular and optokinetic stimuli, consistent upward changes in the gain of these reflexes could be reliably and reproducibly induced in uninjected animals. Floccular injections of sotalol impaired these adaptive changes markedly, whereas injections of isoproterenol enhanced the adaptation, particularly of the VOR measured in darkness. These findings strongly suggest that the effectuation of adaptive changes of vestibular, and possibly other, motor control systems is strongly facilitated by the noradrenergic innervation of the flocculus, which is normally provided by the locus coeruleus (LC), by way of the beta-receptor system, although the activity of this system does not directly affect the signal transmission supporting the basic reflexes as such.

Adaptation, Physiological↗

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↗

PubMed1991

Changes in VOR adaptation after local injection of beta-noradrenergic agents in the flocculus of rabbits.

Noradrenaline (NA) has been implicated as a neuromodulator in plasticity, presumably facilitating adaptive processes. Since the flocculus receives noradrenergic afferents, and ablation of the flocculus interferes with the normal adaptive changes in the VOR gain, experiments were performed to find out whether bilateral injection of monoaminergic substances into the flocculus of rabbits could modify the adaptive changes of the VOR. The visual world surrounding the rabbit was oscillated in opposite direction to the platform on which the rabbit was mounted, which resulted in an adaptive increase in the VOR gain; this adaptation was measured either in light or in darkness. Floccular injection of the beta-agonist isoproterenol did not greatly affect the adaptation of the VOR measured in light. In darkness, however, the increase in gain after injection of isoproterenol was larger than during normal adaptation. The beta-antagonist sotalol reduced the adaptation of the VOR gain significantly in light as well as in darkness. In a control condition without pressure for adaptation (only intermittent testing of the VOR gain over a period of 2.5 h), the gain of the VOR was not significantly affected by similar injections of beta-adrenergic agents. We conclude that the noradrenergic system facilitates the adaptation of the VOR gain to retinal slip in rabbits without affecting the VOR gain directly. At least part of this influence is exerted through beta-receptors located in the cerebellar flocculus.

Adaptation, Physiological↗

PubMed1991

Microinjections of alpha 1- and alpha 2-noradrenergic substances in the cerebellar vermis of decerebrate cats affect the gain of the vestibulospinal reflexes.

1. In addition to mossy and climbing fibers, the Purkinje (P)-cells of the cerebellar cortex receive noradrenergic (NA) afferents which originate mainly from the locus coeruleus. Since these fibers impinge also on the vermal cortex of the cerebellar anterior lobe, which receives a labyrinth input and projects to the lateral vestibular nucleus, experiments were performed in precollicular decerebrate cats to find out whether unilateral injection of alpha-adrenergic substances into the vermal cortex of the cerebellar anterior lobe exerted some influence on posture as well as on the dynamic characteristics of vestibulospinal (VS) reflexes evaluated by recording the multiunit EMG responses of the forelimb extensor triceps brachii of both sides to roll tilt of the animal at 0.15 Hz, +/- 10 degrees. 2. Unilateral injection into the vermal cortex of the culmen of the alpha 1-adrenergic agonist metoxamine or the alpha 2-adrenergic agonist clonidine (0.25 microliters at the concentration of 4 micrograms/microliters of saline) produced a postural asymmetry, characterized mainly by a slight decrease of the extensor tonus in the ipsilateral forelimb and an increased tonus in the contralateral forelimb. The same substances significantly increased the gain (imp./sec/deg) of the first harmonic component of the EMG responses of the ipsilateral and the contralateral triceps brachii to animal tilt. The crossed effects were more prominent for the alpha 2- than for the alpha 1-agonist. However, no significant changes in the phase angle of the responses were observed in both instances. The effects described above occurred within 5-10 min after the injection, reached the peak values after 15-20 min, and disappeared within 2 hours. 3. The postural and reflex changes described above were not due to irritative events following the injection, since they were not observed in control experiments after injection of 0.25 microliter of saline into the same corticocerebellar area prior to the administration of the alpha 1- or the alpha 2-adrenergic agonist. Moreover, the resulting effect were dose-dependent. 4. Both the ipsilateral as well as the contralateral effects induced by the alpha 1- or the alpha 2-adrenergic agonist 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 microliter at the concentration of 8-16 micrograms/microliters in both cases).(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic alpha-Agonists↗

PubMed1991

Microinjections of beta-noradrenergic substances in the cerebellar vermis of decerebrate cats modify the gain of the vestibulospinal reflexes.

1. The noradrenergic (NA) afferent system, which originates mainly from the locus coeruleus and projects to the cerebellar cortex, may act on the corresponding neurons by utilizing not only alpha- but also beta-adrenoceptors. Since the vermal cortex of the cerebellar anterior lobe receives a labyrinth input and projects to the lateral vestibular nucleus (LVN), experiments were performed in precollicular decerebrate cats to find out whether the noradrenergic system intervenes in the control of posture as well as of the dynamic characteristics of vestibulospinal (VS) reflexes elicited by recording the multiunit EMG responses of the forelimb extensor triceps brachii of both sides to roll tilt of the animal at 0.15 Hz, +/- 10 degrees. In particular, we used the method of local microinjection into the vermal cortex of the cerebellar anterior lobe of the non-selective beta-adrenergic agonist ((+/-) -isoproterenol hydrochloride) or antagonist (dl-propranolol hydrochloride) to act on both beta 1- and beta 2-adrenoceptors. 2. Unilateral injection into the vermal cortex of the culmen of isoproterenol (0.25-0.50 microliters at the concentration of 8-16 micrograms/microliter of saline stained with pontamine 5%) decreased the extensor tonus in the ipsilateral forelimb, while the postural activity either remained unmodified or slightly increased in the contralateral fore-limb. The same injection significantly increased the gain (imp./sec/deg) of the first harmonic component of the EMG responses of the ipsilateral and to a lesser extent also of the contralateral triceps brachii to animal tilt. This effect was also associated with slight changes in the phase angle of the responses, which remained positional throughout the experiments. The effects described above occurred within 5-10 min after the injection and reached the highest values after 20-30 min; they were then followed for about 2 hours after the injection, before disappearing. 3. In contrast to these findings, injection in other experiments of 0.25-0.50 microliter of a solution of propranolol at the concentration of 16 micrograms/microliter of saline increased the extensor tonus in the ipsilateral limbs, while the decerebrate rigidity either remained unmodified or slightly decreased in the contralateral limbs. In addition, the amplitude of modulation and thus the response gain of the ipsilateral triceps brachii to the same parameters of animal tilt decreased. This effect was associated with slight changes in the phase angle of the responses. There was also a slight but insignificant decrease in gain of the responses recorded contralaterally to the side of the propranolol injection.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic beta-Agonists↗

PubMed1991

The role of different size vestibulospinal neurons in the static control of posture.

1. In addition to giant cells, originally described by Deiters, the lateral vestibular nucleus contains also medium- and small-size cells. The role that these neurons exert in the static control of posture has been investigated in precollicular decerebrate cats in which the resting discharge of spontaneously active vestibulospinal neurons projecting to lumbosacral segments of the spinal cord (IVS neurons) has been related to the cell size inferred on the basis of the conduction velocity of their axons. 2. In control experiments, the IVS neurons with slower axonal conduction velocity and, by inference, having thinner axons and smaller cell bodies differed from those having faster conduction velocity by displaying a higher resting discharge rate and a relatively regular interspike interval distribution, i.e. a lower coefficient of variation (CV). 3. The resting discharge of the IVS neurons, which corresponded on the average to 24.5 +/- 15.7, S.D. imp./sec, in control experiments, increased significantly to 44.1 +/- 23.8, S.D. imp./sec after ablation of the cerebellar vermis and the fastigial nuclei, leading to a great increase in postural activity, while the proportion of regularly discharging units (with the lowest CV) increased. Moreover, the negative correlation between resting discharge of all the recorded IVS neurons and the conduction velocity of the corresponding axons, which was quite slight in the experiments with the cerebellum intact, greatly increased after partial cerebellectomy. This finding was due to a prominent increase in resting discharge of the small-size IVS neurons, while the discharge of the large-size IVS neurons was, on the average, comparable to that obtained in the controls. It appears, therefore, that the cerebellum exerts a prominent tonic inhibitory influence on the small-size IVS neurons, which are thus responsible for the great increase in decerebrate rigidity after cerebellectomy. 4. The resting discharge rate of the IVS neurons was not, on the average, greatly modified after ipsilateral acute (aVN) and chronic vestibular neurectomy (cVN) with respect to the controls. However, the proportion of regularly discharging units (with the lowest CV) decreased after aVN, but increased after cVN. The relation found in control experiments, i.e. the faster the conduction velocity of VS axon the lower was the unit discharge at rest, was lost after aVN, due to a decrease in resting discharge rate of the slow neurons. The mean discharge rate of these units, however, recovered after cVN, so that the negative correlation between resting discharge rate and axonal conduction velocity was reestablished.(ABSTRACT TRUNCATED AT 400 WORDS)

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PubMed1990

Injection of a cholinergic agonist in the dorsolateral pontine tegmentum of cats affects the posturokinetic responses to cortical stimulation.

Microinjection into the dorsolateral pontine tegmentum of the muscarinic agonist bethanechol, leading to activation of cholinoceptive pontine reticular formation (pRF) neurons and the related medullary inhibitory reticulospinal system, did not modify the threshold, latency and amplitude of the forelimb flexion elicited by unilateral stimulation of the corresponding motor cortex. However, the remaining limbs which displayed a diagonal pattern of postural adjustments showed a dissociation of their postural responses in 2 components: the early component of central origin greatly decreased in amplitude, while the late component attributed to reflex mechanism triggered by the unbalance brought about by the flexion movement increased. Further evidence indicated that the pRF system intervenes in the gain regulation of the early postural responses during the cortically induced limb movement.

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