O. Pompeiano

The lateral reticular nucleus in the cat—I. An experimental anatomical study of its spinal and supraspinal afferent connections

The localization of the neurons from which the main ascending and descending projections to the lateral reticular nucleus originate has been studied in nine cats, using the retrograde axonal transport of horseradish peroxidase injected within that nucleus. The ascending spinoreticular neurons are widely distributed from the cervical to the sacral segments of the spinal cord. These neurons, which are of different sizes, are mainly located within Rexeds laminae VI, VII and VIII, but they spread both dorsally to laminae II–VI as well as ventrally to lamina IX. Labeled neurons of a size similar to motoneurons are particularly found within lamina IX, intermingled with the motoneurons. The spinal projection to the lateral reticular nucleus is crossed and uncrossed, with the ipsilateral spinoreticular neurons being located more dorsally within the grey matter of the spinal cord than the contralateral spinoreticular neurons. Moreover, while neurons with a crossed ascending projection are almost equally distributed along the whole rostro-caudal extension of the spinal cord, those with an uncrossed projection are predominantly located within the cervical segments of the spinal cord. Additional evidence indicates that the spinoreticular projection to the lateral reticular nucleus is somatotopically organized. In addition to the spinoreticular projection, the lateral reticular nucleus receives a crossed rubroreticular projection and a crossed fastigioreticular projection originating from the rostro-ventralmost part of the nucleus. A few neurons in the interposite nuclei also project to the lateral reticular nucleus.

C-Fos expression in the rat brain after unilateral labyrinthectomy and its relation to the uncompensated and compensated stages

The expression of the immediate early gene c-fos has been studied in the entire brain of rats 3, 6 and 24 h after surgical unilateral labyrinthectomy. We combined in situ hybridization for c-fos messenger RNA with immunocytochemistry for Fos protein to document very early changes in c-fos expression and to identify with cellular resolution neuronal populations activated by unilateral labyrinthectomy. Three hours after unilateral labyrinthectomy a bilateral increase in both c-fos messenger RNA and protein levels was seen in the superior, medial and spinal vestibular nuclei, nucleus Y, and prepositus hypoglossal nucleus. These changes were asymmetric in the medial vestibular nucleus, being most prominent in the dorsal part of the contralateral nucleus (where second order vestibular neurons are located) and in the ventral part of the ipsilateral nucleus (where commissural neurons acting on the medial vestibular nucleus of the intact side are located). An increase in c-fos messenger RNA expression was seen bilaterally, but with an ipsilateral predominance, in the vermal and paravermal areas of the cerebellar cortex, flocculus and paraflocculus, as well as in the precerebellar lateral and paramedian reticular nuclei. c-fos messenger RNA and protein levels increased in a few regions of the contralateral inferior olive. A predominantly ipsilateral increase in c-fos expression also occurred in the caudate-putamen. A bilateral but not exactly symmetric increase in both c-fos messenger RNA and protein levels was present in several nuclei of the dorsal pontine tegmentum (parabrachial nucleus, locus coeruleus and laterodorsal tegmental nucleus), mesencephalic periaqueductal gray, and several hypothalamic, thalamic and cerebrocortical regions. No change was seen in the cerebellar nuclei, lateral vestibular nucleus and red nucleus. The increased expression of c-fos observed 3 h after unilateral labyrinthectomy, in conjunction with the sudden occurrence of postural and motor deficits, usually declined 6-24 h after the lesion, i.e. during the development of vestibular compensation. In the dorsal part of the medial vestibular nucleus, however, the pattern of c-fos expression observed 3 h after unilateral labyrinthectomy was reversed 6-24 h after the lesion: both c-fos messenger RNA and protein levels increased on the ipsilateral side, but greatly decreased on the contralateral side. In conclusion, asymmetric changes in c-fos expression occurred within 3 h after unilateral labyrinthectomy, but gradually declined or reversed 6 and 24 h after the lesion, thus being temporally related to the appearance and development of vestibular compensation.

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 LCs 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 LCs suppression of the recurrent inhibition pathway as well as by its presynaptic facilitation of afferent impulse transmission at the spinal cord level.

Responses of purkinje cells of the cerebellar vermis to neck and macular vestibular inputs

Abstract1.The dynamic analysis of the control exerted by neck and macular vestibular receptors on the cerebellar cortex has been investigated in precollicular decerebrate cats submitted to sinusoidal rotation along the longitudinal axis of the animal at the frequency of 0.026 Hz and at peak amplitudes up to 10° for the neck input and 15° for the macular input.2.Purkinje (P) cells located in the vermal cortex of the cerebellar anterior lobe, particularly in the longitudinal parasagittal zone which projects to the ipsilateral lateral vestibular nucleus (LVN), showed a sinusoidal modulation of the firing rate in response to sinusoidal stimulation of the neck receptors or the vestibular receptors, the phase of the responses being in most units related to the extreme neck or head position. Mossy fiber (MF) and/or climbing fiber (CF) responses of the same or different P-cells to the two inputs were observed.3.The sensitivity of the MF-response of the P-cells to the neck input, elicited by sinusoidal rotation of the neck and expressed in per cent of the average firing rate per degree of neck rotation, corresponded on the average to 2.71±1.67, S. D. This value was significantly higher than that of the MF-response of the P-cells to the macular input elicited by sinusoidal tilt along the longitudinal axis of the whole animal, which corresponded to 1.71±1.01, S.D.4.Most of the MF-responses of the P-cells to the neck input were characterized by an excitation during side-down rotation of the neck and by an inhibition during side-up rotation, whereas most of the MF-responses of the P-cells to the macular input showed just the opposite behavior, being inhibited by side-down tilt of the animal and excited by side-up tilt.5.Units which received a convergent input from both neck and macular receptors and showed an antagonistic pattern of response to the two inputs were tested during rotation of the head alone, in order to excite simultaneously the two kinds of receptors. Due to the higher sensitivity of the neck over the macular response, the magnitude of the combined response tended to be similar to the difference between the individual ones. Moreover, the phase of the resulting response was always modified with respect to that of the response to the neck input alone, and became in some instances related to velocity of neck rotation rather than to neck position.6.These findings indicate that opposite responses to neck and macular inputs occur at corticocerebellar level. However, a final integration of the two inputs, leading to suppression of the conflicting responses, may occur either at medullary (LVN) or at spinal cord level.

Fastigiofugal fibers to the lateral reticular nucleus; An experimental study in the cat

Abstract Total or partial lesions of the fastigial nucleus were made in thirteen cats and the ensuing preterminal and terminal degeneration in the lateral reticular nucleus ( nucleus funiculi lateralis ) studied in silver-impregnated sections by methods of Nauta and Glees. The results obtained by the two methods are concordant. The fibers terminating within the lateral reticular nucleus probably originate from the rostral third of the fastigial nucleus only. They pass within the hook bundle and reach the contralateral lateral reticular nucleus from the reticular formation dorsal to this. The fibers are distributed to certain areas of the “spinal” as well as the “supraspinal” part of the nucleus and make synaptical contacts with perikarya and cell processes of small as well as large cells. The anatomical connections described constitute a link in a pathway by which the cortex of the anterior lobe vermis is enabled to influence extensive areas of the contralateral cerebellar cortex, comprising functionally different regions.

Coerulospinal influence on recurrent inhibition of spinal motonuclei innervating antagonistic hindleg muscles of the cat

The locus coeruleuss (LCs) effect on recurrent inhibition of gastrocnemius-soleus (GS) and common peroneal (CP) monosynaptic reflexes (MSRs) was demonstrated to exceed the concomitant facilitation, indicating the independency of LCs disinhibition and facilitation measures in this study. In contrast, the disinhibition effect correlated closely with the recurrently inhibited MSRs. The disinhibition phenomenon was also accompanied by progressive delay and diminution in the Renshaw cell field potential. Hence, the recovery of recurrently inhibited MSRs was probably due, in part at least, to the LCs inhibition of the related Renshaw cell activity. Furthermore, the site-specific, discordant changes in the disinhibition of GS, compared with CP MSRs, as revealed by tracking studies imply that representations of these antagonistic motonuclei may occupy different LC loci. Accordingly, the nonuniform disinhibition may be due to the activation of discrete aggregates of LC neurons which are responsible predominantly in controlling the recurrent inhibitory pathway belonging to one or the other of the antagonistic motonuclei. These findings support a differential LC inhibitory control of Renshaw cell activity, releasing the related motoneurons for the Ia synaptic transmission — a disinhibitory process that is crucial for the LCs independent control of the recurrent circuit of antagonistics extensor and flexor motoneurons.

Injections of β-noradrenergic substances in the flocculus of rabbits affect adaptation of the VOR gain

SummaryNoradrenaline (NA) has been implicated as a neuromodulator in plasticity, presumably facilitating adaptive processes. Recent experiments by others have suggested a modulatory role of NA in adaptive changes in the vestibulo-ocular reflex (VOR). These experiments showed that general depletion of brain NA resulted in a decreased ability to produce adaptive changes in the VOR gain. In order to identify the specific brain region responsible for these effects, as well as the nature of the adrenoceptors involved, we injectedβ-adrenergic substances bilaterally into the flocculus of rabbits. The flocculus is known to receive noradrenergic afferents and, moreover, ablation of the flocculus interferes strongly with the normal adaptive changes in the VOR gain. We injected theβ-agonist isoproterenol and theβ-antagonist sotalol, and compared the adaptive capacity of the rabbits after these injections to that in a situation without injection. The rabbit was oscillated in a direction opposite to the direction of motion of the platform on which the rabbit was mounted, a condition which normally results in an increase in the VOR gain, measured either in light or in darkness. Injection of theβ-agonist did not greatly affect the adaptation of the VOR measured in the light. In darkness, the increase in gain after the injection of isoproterenol was larger than in the non-injection experiments in 9 out of 10 rabbits. Theβ-antagonist sotalol reduced the adaptation of the VOR gain significantly in the 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 either remained unaffected or was only slightly affected by similar injections ofβ-adrenergic agents in individual rabbits. For the group as a whole, these effects were insignificant. We conclude from these results that noradrenergic systems facilitate 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 throughβ-receptors located in the cerebellar flocculus.

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)

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.

Spinovestibular relations: anatomical and physiological aspects.

Publisher Summary Anatomical observations have shown that the spinovestibular pathway originates mainly from the lumbosacral levels of the spinal cord. Their fibers ascend with those of the dorsal spinocerebellar tract along the dorsal part of the lateral funiculus. Direct spinovestibular fibers and collaterals of the dorsal spinocerebellar tract terminate in very small numbers in the caudalmost regions of the medial and descending vestibular nuclei, and in the hindlimb region of the lateral vestibular nucleus, while an abundant projection impinges upon the nuclei x and z of Brodal and Pompeiano. Recent observations indicate in fact that this nucleus represents the medullary relay in the low threshold group I muscular path from the hindlimb to the cerebral cortex. Somatic afferent impulses, however, may reach the vestibular nuclei indirectly, either via the reticular formation or the cerebellum. The spinal influence on the vestibular nuclei mediated through the reticular formation is mainly an excitatory one. Cutaneous and high threshold (group II and III) muscular afferents, which are responsible for the ipsilateral flexion reflex at segmental level, are particularly able to modify the spontaneous activity of these vestibular neurons. On the contrary, the low threshold group I muscle afferents are apparently ineffective. Experiments of natural stimulation of different types of receptors indicate that skin and deep receptors, particularly the joint receptors, may excite the vestibular neurons.