Organization of the crossed tecto-reticulo-spinal projection in rat--II. Electrophysiological evidence for separate output channels to the periabducens area and caudal medulla

The previous paper (Redgrave et al., Neuroscience 37, 571-584, 1990) presented anatomical evidence indicating there are at least two largely segregated components of the crossed tecto-reticulo-spinal pathway which project to the periabducens area and caudal medulla. An immediate question arising from this finding is whether tectal cells which project either to the periabducens area or to the caudal medulla have different electrophysiological response properties. An answer to this question would be relevant to the issue of whether different components of the tecto-reticulo-spinal system are specialized for the production of different classes of orienting movement. Accordingly, extracellularly recorded units in the superior colliculus of urethane anaesthetized rats were tested for antidromic activity following electrical stimulation of the periabducens area or the caudal medulla. When antidromic potentials were successfully recorded the sensory properties of the units were tested with a range of unimodal visual, somatosensory and auditory stimuli. The following results were obtained. (i) Tectal cells antidromically activated by stimulation of the caudal medulla were preferentially sensitive to somatosensory stimuli from the perioral region, while cells activated from the periabducens area were more frequently responsive to auditory stimuli. (ii) Tectal fibres activated by stimulation of the caudal medulla had significantly higher conduction velocities than the fibres activated by electrodes in the periabducens region. (iii) More than 90% of antidromically activated cells were located in stratum album intermediale or dorsal stratum profundum. These electrophysiological findings confirm and extend previous anatomical observations which indicate that components of the crossed descending projection of the colliculus may be functionally specialized for the production of different classes of orienting movements.     

Anatomical and physiological evidence for a cerebellar nucleo-cortical projection in the cat

Combined neuroanatomical and electrophysiological experiments were performed to test the hypothesis that axon collaterals of neurons in the cerebellar nuclei project to the cerebellar cortex in cats. The anatomical studies demonstrated that (a) following the injection of tritiated leucine into the deep cerebellar nuclei, labeled fibers could be traced into the granular layer of the cerebellar cortex, and (b) following the injection of horseradish peroxidase into the cerebellar cortex, retrogradely labeled horseradish peroxidase-positive neurons were identified in the deep nuclei. The electrophysiological experiments confirmed the anatomical findings. Neurons in the dentate and interposed nuclei, identified by their antidromic activation from the brachium conjunctivum, could also be activated antidromically from the cerebellar surface. Collision experiments demonstrated that projections from the deep cerebellar nuclei to the cerebellar cortex are in part collaterals of efferent neurons projecting through the brachium conjunctivum. Care was taken to ensure that all recordings were obtained from the region of cell somata in order to minimize the likelihood of recording from neuronal elements passing through the cerebellar nuclei. These combined neuroanatomical and electrophysiological studies provide strong evidence supporting the existence of a collateral system from cerebellar output neurons to the cerebellar cortex. The existence of this collateral system emphasizes that the cerebellar cortex and cerebellar nuclei may comprise a functional unit in which these collaterals may serve as a substrate for feedback control of the cerebellar cortex by the cerebellar output.     

Visual,auditory and somatosensory convergence in output neurons of the cat superior colliculus: multisensory properties of the tecto-reticulo-spinal projection

Summary A select population of superior colliculus (SC) neurons receives and integrates information from the visual, auditory and somatosensory systems. Determining which SC neurons comprise this population and where they send their multisensory messages is important in understanding the functional impact of the SC on attentive and orientation behavior. One of the major routes by which the SC influences these behaviors is the tecto-reticulo-spinal tract, a descending pathway that plays an integral role in the orientation of the eyes, ears and head. Of the 182 tecto-reticulo-spinal neurons (TRSNs) encountered in the present study, almost all (94%) responded to sensory stimuli and the overwhelming majority (84%) were multisensory. The present results demonstrate that the TRSN serves as an important link among the different sensory systems and provides a substrate through which they may gain access to the circuitry mediating orientation behavior.     

Topographical organization of the nigrotectal projection in rat: evidence for segregated channels.

Recent evidence suggests that projections from the superior colliculus to the brainstem in rat are organized into a series of anatomically segregated output channels. To understand how collicular function may be modified by the basal ganglia it is important to know whether particular output modules of the superior colliculus can be selectively influenced by input from substantia nigra. The purpose of the present study was, therefore, to examine in more detail topography within the nigrotectal system in the rat. Small injections (10-50 nl) of a 1% solution of wheatgerm agglutinin conjugated with horseradish peroxidase were made at different locations within substantia nigra and surrounding structures. A discontinuous puff-like pattern of anterogradely transported label was found in medial and caudal parts of the ipsilateral intermediate layers of the superior colliculus. In contrast, the rostrolateral enlargement of the intermediate layers contained a greater density of more evenly distributed terminal label. Injection sites associated with this dense pattern of laterally located label were concentrated in lateral pars reticulata, while the puff-like pattern was produced by injections into ventromedial pars reticulata. Retrograde tracing experiments with the fluorescent dyes True Blue and Fast Blue revealed that injections involving the rostrolateral intermediate layers were consistently associated with a restricted column of labelled cells in the dorsolateral part of ipsilateral pars reticulata. Comparable injections into medial and caudal regions of the superior colliculus produced retrograde labelling in ventral and medial parts of the rostral two-thirds of pars reticulata. Both anterograde and retrograde tracing data indicated that contralateral nigrotectal projections arise from cells located in ventral and medial pars reticulata. The present results suggest that the main ipsilateral projection from substantia nigra pars reticulata to the superior colliculus comprises two main components characterized by regionally segregated populations of output cells and spatially separated zones of termination. Of particular interest is the apparent close alignment between terminal zones of the nigrotectal channels and previously defined populations of crossed descending output cells in the superior colliculus. Thus, the rostrolateral intermediate layers contain a concentration of terminals specifically from dorsolateral pars reticulata and output cells which project to the contralateral caudal medulla and spinal cord. Conversely, the medial and caudal intermediate layers receive terminals from ventral and medial pars reticulata and contain cells which project specifically to contralateral regions of the paramedian pontine and medullary reticular formation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Hypovolemic shock: critical involvement of a projection from the ventrolateral periaqueductal gray to the caudal midline medulla

Previous research has suggested that the ventrolateral column of the periaqueductal gray (vlPAG) plays a crucial role in triggering a decompensatory response (sympathoinhibition, hypotension, bradycardia) to severe blood loss. vlPAG excitation triggers also quiescence, decreased vigilance and decreased reactivity, the behavioral response which usually accompanies hypovolemic shock. The aim of this study was to identify, in unanesthetized rats, the main descending pathway(s) via which vlPAG neurons trigger sympathoinhibition and bradycardia in response to severe blood loss. Firstly, immediate early gene (c-Fos) expression was used to identify vlPAG neurons selectively activated by severe blood loss. Subsequently, the specific medullary projections of these vlPAG neurons were defined by combined c-Fos, retrograde tracing (double-label) experiments. It was found that vlPAG neurons selectively activated by severe hemorrhage project overwhelmingly to the vasodepressor portion of the caudal midline medulla (CMM). Previous studies indicate that this CMM region mediates behaviorally-coupled cardiovascular adjustments and the findings described here fit with the idea that CMM neurons are uniquely recruited by salient challenges, the adaptive responses to which require more than reflexive homeostatic cardiovascular adjustments.     

A pressor area in the caudal part of the ventral surface of the medulla

Department of Physiology of Visceral Systems, Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR B. I. Tkachenko.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 106, No. 10, pp. 387–389, October, 1988.     

Anatomical and electrophysiological evidence for a direct projection from ammon's horn to the medial prefrontal cortex in the rat

Summary Following microinjection of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) into the medial prefrontal cortex (defined as the neocortical area innervated by the thalamic mediodorsal nucleus) labelled cells were observed in the pyramidal layer of the CA1 field of Ammon's horn. Observations made using antidromic stimulation confirmed these results, and revealed the slow conduction velocity of the fibres of the hippocampal cells innervating the prefrontal cortex. Taken together, these data provide evidence for a direct projection of CA1 cells to the medial prefrontal cortex.     

Cardiorespiratory responses to chemical stimulation of the caudal most ventrolateral medulla in the cat.

Chemical stimulation of caudal ventrolateral medulla evoked both pressor and depressor responses. The pressor sites were generally located caudal to depressor sites. Effects on heart rate were variable. Significant increases in minute ventilation were also observed, which were primarily due to changes in respiratory frequency.     

Anatomical evidence for multiple pathways leading from the rostral ventrolateral medulla (nucleus paragigantocellularis) to the locus coeruleus in rat

Using retrograde transport of Fluoro-Gold (FG) combined with immunofluorescence for phenylethanolamine-N-methyltransferase (PNMT), we have examined afferents to the nucleus locus coeruleus (LC) from the rostral ventrolateral medulla (nucleus paragigantocellularis; PGi) in rats sustaining lesions of the medullary adrenergic bundle (MB). In lesioned rats, very few adrenergic LC-projecting neurons persist in the PGi ipsilateral to the lesion, representing a 90% decrease in comparison to non-lesioned animals. These results indicate that almost all adrenergic input to the LC from C1 neurons in PGi is conveyed by the MB. In contrast, the number of non-adrenergic LC afferent neurons in the PGi ipsilateral to the lesion only decreased by 48% after such lesions. Thus, this pathway also provides non-adrenergic projections to LC from PGi, but many of these are conveyed by other route(s) as well.     

Development and retraction of a crossed retinal projection to the inferior colliculus in neonatal pigmented rats.

A transient aberrant projection from the retina to the contralateral inferior colliculus was demonstrated in pigmented rats in both whole-brains and sections following intra-ocular injection of horseradish peroxidase. The projection was prominent on the day of birth but reached its maximum density and extent after injection on day 1, when it covered at least a third of the inferior colliculus. It was absent or nearly absent by day 5. Its consistency, size, orderliness and systematic retraction suggest that it is not merely a developmental accident.     

Immunohistochemical evidence for a crossed cholecystokinin corticostriatal pathway in the rat.

Using the indirect immunofluorescence technique, the effects of decortication and callosotomy on the pattern of cholecystokinin (CCK)-like immunoreactivity were studied in the striatum of the rat. Decortication plus callosotomy, but not decortication alone, caused a strong decrease in the immunoreactivity on the side ipsilateral to the lesion. An almost complete disappearance of CCK immunoreactive patches in the medial-dorsal aspects of the striatum was observed. These results indicate that part of the striatal CCK immunoreactive fibres are of cortical origin, to a considerable extent from the contralateral side.     

Retinal topography of the neonatal crossed aberrant exuberant projection to the inferior colliculus in the pigmented rat.

The retinal topography of the neonatal transient projection to the inferior colliculus was investigated in pigmented rats by injecting the retrograde fluorescent tracer Fast Blue into the colliculi. The results show that the projection arises from a small population of ganglion cells scattered across the entire contralateral retina, and that the transient projection is therefore not merely an overshoot of axons from the peripheral nasal retina whose appropriate target is the caudal pole of the superior colliculus.     

Sympathetic and metabolic mechanisms of the cerebrovasomotor function of the caudal ventrolateral medulla in rats.

We attempted to elucidate the cerebrovasomotor function of the caudal ventrolateral medulla. Sixty-one rats were anaesthetized, paralysed and artificially ventilated. The microsphere method was employed for the measurement of blood flow. Microinjection of an antagonist of excitatory amino acids, kynurenate (2 nmol), into functionally identified depressor sites within the caudal ventrolateral medulla produced arterial hypertension of about 140 mmHg. We found that the cerebral blood flow was substantially increased, but was maintained at the same level (17 rats) as that observed under phenylephrine-induced hypertension (26 rats). Bilateral severing of the cervical sympathetic trunks resulted in a further increase in blood flow in all brain regions studied (18 rats). The response was most significant in the cerebral parasagittal cortex (164 +/- 31% of baseline without, and 211 +/- 43% with sympathectomy; mean +/- S.D.; P < 0.001). The contributions of the cerebral metabolic mechanism to this flow increase under denervation was minimal, as evidenced by the observation of disproportionately smaller changes in cerebral metabolic rate for oxygen during any type of hypertension. We conclude that the cerebrovasomotor functions of the caudal ventrolateral medulla may operate to keep an equilibrium between simultaneously working tonic inhibitions against sympathetic vasoconstriction as well as against vasodilatation. This dual effect is mediated by excitatory amino acid receptors located within this particular brain area. The vasodilator mechanism may be of neurogenic origin. When the function of the brain area is suppressed, the subsequently disinhibited vasodilator mechanism dominates the cerebrovascular autoregulatory function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Modulation of the sympathetic response to acute hypoxia by the caudal ventrolateral medulla in rats

Hypoxia elevates splanchnic sympathetic nerve activity (SNA) with differential effects during inspiration and expiration by unresolved central mechanisms. We examined the hypothesis that cardiovascular-related neurones in the caudal ventrolateral medulla (CVLM) contribute to the complex sympathetic response to hypoxia. In chloralose-anaesthetized, ventilated, vagotomized rats, acute hypoxia (10% O₂, 60 s) evoked an increase in SNA (103 ± 12%) that was characterized by a decrease in activity during early inspiration followed by a prominent rise during expiration. Some recorded baro-activated CVLM neurones ( n = 13) were activated by hypoxia, and most of these neurones displayed peak activity during inspiration that was enhanced during hypoxia. In contrast, other baro-activated CVLM neurones were inhibited during hypoxia ( n = 6), and most of these neurones showed peak activity during expiration prior to the onset of hypoxia. Microinjection of the glutamate antagonist kynurenate into the CVLM eliminated the respiratory-related fluctuations in SNA during hypoxia and exaggerated the magnitude of the sympathetic response. In contrast, microinjection of a GABA_A antagonist (bicuculline or gabazine) into the CVLM dramatically attenuated the sympathetic response to hypoxia. These data suggest the response to hypoxia in baro-activated CVLM neurones is related to their basal pattern of respiratory-related activity, and changes in the activity of these neurones is consistent with a contribution to the respiratory-related sympathetic responses to hypoxia. Furthermore, both glutamate and GABA in the CVLM contribute to the complex sympathetic response to acute hypoxia.     

Hyaluronate-proteoglycan complex: evidence for separate biosynthesis mechanisms of the macromolecules.

In cartilage cells biosynthesis of hyaluronate and chondroitin-4-,-6-sulfate from proteoglycan takes place via two different distinct precursor pools; the synthesis of hyaluronate appears to require the unaffected formation of nucleotides and nucleic acids, whereas that of proteoglycan is very sensitive to the modulation of protein biosynthesis.     

Anatomical evidence that the pontine lateral tegmental field projects to lamina I of the caudal spinal trigeminal nucleus and spinal cord and to the Edinger-Westphal nucleus in the cat

Autoradiographical tracing results in the cat indicate that the lateral pontine tegmental field projects mainly contralaterally to the marginal layer of the spinal trigeminal nucleus, to laminae I and II and the lateral part of laminae V and VI of the spinal cord and the Edinger-Westphal nucleus. It is pointed out that the projections from the lateral pontine tegmentum are very similar to the ones derived from the Edinger-Westphal nucleus and that these two areas are reciprocally connected. It is postulated that both areas may play a role in supraspinal pain control.     

Collateralization of projections from the rostral ventrolateral medulla to the rostral and caudal thoracic spinal cord in felines

Stimulation of vestibular receptors elicits distinct changes in blood flow to the forelimb and hindlimb, showing that the nervous system has the capacity to produce changes in sympathetic outflow which are specific for a particular region of the body. However, it is unclear whether the rostral ventrolateral medulla (RVLM), the primary region of the brainstem that regulates sympathetic outflow to vascular smooth muscle, has the appropriate connectivity with sympathetic preganglionic neurons to generate anatomically patterned responses. To make this determination, the retrograde fluorescent tracer Fast Blue was injected into the T₄ spinal cord segment of cats, which regulates upper body blood flow, whereas Fluoro-Ruby was injected into the T₁₀ segment to label projections to a region of the spinal cord that regulates lower body blood flow. More neurons were single-labeled by a particular tracer (92 %) than were double labeled by both tracers (8 %), supporting the notion that the RVLM can regulate sympathetic outflow from a limited number of spinal cord segments. Since a large fraction of RVLM neurons that control sympathetic outflow in rodents contain epinephrine, we additionally determined whether the tracer-labeled cells were immunopositive for the enzyme tyrosine hydroxylase (TH), which participates in the synthesis of catecholamines. Double labeling by the two tracers injected into the spinal cord was more common for TH-immunopositive neurons than for the general population of RVLM neurons: 19 % of the TH-positive cells contained both Fast Blue and Fluoro-Ruby, 30 % contained one of the tracers, and 51 % were not labeled by either tracer. Furthermore, many spinally projecting neurons in close proximity to the RVLM catecholaminergic neurons (41 % of the population) were not immunopositive for TH, suggesting that feline RVLM is neurochemically heterogeneous.     

The crossed projection from the temporal retina to the dorsal lateral geniculate nucleus in the rat

The crossed projection from the temporal crescent in the rat's retina was studied by producing a discrete retinal lesion in one eye and examining the dorsal lateral geniculate nucleus and superior colliculus contralateral to the lesion for anterograde degeneration products. The position of this crossed degeneration was described in relation to the uncrossed retinal termination in the same structures by injecting the opposite eye with [³H]proline and processing the tissue for autoradiography. The location of the retinal lesion in relation to the temporal cresent was identified by injecting the dorsal lateral geniculate nucleus ipsilateral to the lesioned eye with a fluorescent tracer, to retrogradely label the ipsilaterally projecting retinal ganglion cells in the lesioned eye.

Retinal lesions that were histologically verified to be restricted to the temporal crescent produced crossed degeneration in the superior colliculus at its rostral border, in accord with this projection's published visual topography. These same lesions consistently yielded a very circumscribed and sparse amount of degeneration in the contralateral dorsal lateral geniculate nucleus at its dorsomedial border, abutting the optic tract dorsally and the lateroposterior nucleus medially. The degeneration bore no consistent relationship to the position of the uncrossed retinal terminal field, which is situated further 9ventrally in the dorsal lateral geniculate nucleus; rather, this crossed temporal projection terminated in the outer shell of the nucleus along its medial border.

This crossed temporal retinogeniculate projection, together with the crossed projection from nasal retina, forms a continuous map of the complete contralateral retina in the outer shell of the dorsal lateral geniculate nucleus, likely to arise from a population of retinal ganglion cells possessing small soma sizes. This dorsomedial part of the rat's dorsal lateral geniculate nucleus, receiving a crossed projection from the temporal retina, may by similar to the cat's lamina 3 in the medial interlaminar nucleus of its retinogeniculate pathway. This result clarifies the homologous subdivisions of the dorsal lateral geniculate nucleus in the rodent and feline thalamus.