Autoradiographic studies of the projections of the midbrain reticular formation: descending projections of nucleus cuneiformis.

The descending projections of nucleus cuneiformis in the cat were traced by autoradiography in the transverse and sagittal planes following stereotaxically placed injections of 3H-leucine. Many descending axons are organized into distinct fiber systems, of which the largest and most well-defined crosses directly in the midbrain and descends through the ventromedial tegmentum of the brain stem. This fiber system first terminates profusely in n. reticularis tegmenti pontis and then proceeds through the rhombencephalic tegmentum emitting transversely oriented branches to n. reticularis pontis caudalis and gigantocellularis, the raphe magnus and the facial nucleus...

The commissural projection of the superior colliculus in the cat.

The origin, course, and termination of the commissural projection of the superior colliculus were studied using the orthograde and autoradiographic tracing method and the retrograde method utilizing horseradish peroxidase. The complementary and mutually confirming sets of data showed that the commissural fibers interconnect a restricted region of the colliculi. This region includes the strata grisea intermedium and profundum and to a lesser degree the stratum opticum. It extends throughout only the rostral part of the colliculus where it ends abruptly at a level slightly less than half the distance from the anterior border of the deep gray layers. By using the needle used for isotope injection to record multiunit responses to somatic and visual stimuli, direct evidence was obtained that this region falls within that functional area of the colliculus devoted to face representation and central vision. The results also suggested that more commissural fibers arise from lateral than medial parts of this region and that many fibers interconnect corresponding points in the colliculi. In addition to intertectal connections, the commissural projection contains decussating axons which terminate in tegmental structures and within a restricted zone of the central gray matter directly overlying the oculomotor complex. The results are discussed in relation to the possible role the commissural projection plays in the regulation of eye and head movement.

The superior colliculus control of pinna movements in the cat: possible anatomical connections.

Possible anatomical pathways mediating superior colliculus control of pinna movements were determined in the cat using the orthograde autoradiographic tracing method and the retrograde horseradish peroxidase technique. This was done in the following manner. First, the division of the facial nucleus that innervates the pinna muscles was determined by injecting the pinna muscles with HRP and surveying the facial nucleus for retrogradely filled cells. Second, the brainstem regions that project the facial nucleus were identified using the horseradish peroxidase method. Third, the superior colliculus projections to these areas were studied using the autoradiographic tracing method. The results suggest that superior colliculus control of pinna movements is mediated entirely by indirect connections with the facial nucleus and that these connections occur mainly in a paralemniscal zone in the lateral midbrain. Of all the brainstem regions shown by the horseradish peroxidase experiments to project to the facial nucleus only this midbrain paralemniscal zone received a projection from the superior colliculus that was dense and overlapped precisely the region containing facial projecting neurons. Further autoradiographic tracing revealed that the facial nucleus was the primary brainstem target of this paralemniscal zone and that all paralemniscal fibers projecting to the facial nucleus ended in the subdivision that innervates the pinna muscles. Other paralemniscal efferents terminate in the opposite paralemniscal zone. The data suggest that other connections between the superior colliculus and the facial nucleus may occur in the cuneiform nucleus of the midbrain, the region around the oculomotor complex, and the reticular formation dorsal to the superior olive.

Superior colliculus connections with the extraocular motor nuclei in the cat.

Direct and indirect projections from the cat superior colliculus to the extraocular motor nuclei were studied using the orthograde autoradiographic tracing method, the retrograde horseradish peroxidase technique, and Golgi methods. The results show that the superior colliculus projects to the central gray matter directly overlying the oculomotor complex. This projection arises almost entirely from the rostral third of the colliculus, and it terminates most heavily over the rostral half of the oculomotor complex. Dendrites of oculomotor cells extend into this tectal termination zone, making direct tecto-oculomotor contacts possible. Central gray cells within this termination zone project bilaterally to the abducens nuclei. It is proposed that the superior colliculus projection to the supraoculomotor central gray matter and the projection from the central gray matter to the abducens nuclei play a role in convergent eye movements. The superior colliculus projects lightly to a cell group directly ventrolateral to the trochlear nucleus. The superior colliculus sends a small direct projection to the contralateral abducens nucleus and a substantial projection to wide regions of the reticular formation that have been shown previously to project, in turn, to the abducens nucleus. Colliculus cells projecting to the abducens nucleus and adjacent reticular formation are located only in the caudal three-fourths of the colliculus, where they become increasingly concentrated at successively more caudal levels. It is proposed that the graded density of the cells of origin of this projection is the basic structural mechanism by which the colliculus generates horizontal foveating saccades of different amplitudes. Laminar analysis of the origin of all the superior colliculus projections to the extraocular motor regions described here revealed that they arise mostly from the stratum griseum intermedium.

Autoradiographic studies of the projections of the midbrain reticular formation: ascending projections of nucleus cuneiformis.

The ascending projections of the cuneiform nucleus in the cat were traced by autoradiography in the transverse and sagittal planes following stereotaxically placed injections of (3)H-leucine. The ascending fibers are almost exclusively ipsilateral and enter the diencephalon as a wide radiation. At the mesodiencephalic junction fibers enter the nucleus of the posterior commissure and pretectal nuclei, and others cross in the posterior commissure to distribute to these structures on the contralateral side. More ventrally directed fibers distribute to the fields of Forel and then spread into the posterior hypothalamus and zona incerta. At the caudal level of the ventral thalamic group, the ascending fibers diverge and follow two separate courses. One division of fibers continues forward beneath the ventral thalamic group and distributes to the zpna incerta and dorsal hypothalamic area. It rapidly diminishes in size as it attains more rostral levels where it is found in the bed nuclei of the stria terminalis and the anterior commissure. Other fibers of this division spread laterally to innervate the ventral lateral geniculate nucleus, the lateral hypothalamus, and preoptic area, and still others follow the entire confirmation of the thalamic reticular nucleus. The second division of fiber ascends through midline and intralaminar nuclei, completely encircling the mediodorsal nucleus, which is uninnervated except for a small ventral region. The distribution of this division is heaviest to the paraventricular, parafascicular, and central dorsal nuclei. Neither division is conspicuous rostral to the anterior commissure. No projections to neostriatum or specific thalamic nuclei were evident.

Efferent projections of the neonatal cat superior colliculus: facial and cerebellum-related brainstem structures.

The superior colliculus develops its influence over eye and pinna movements gradually during postnatal maturation. Because superior colliculus cells respond earlier in postnatal life to nonvisual than to visual cues, it seemed likely that efferents involved in pinna movements would develop earlier than those involved in eye movements. In the present study, we examined the projections of the superior colliculus to structures related to the cerebellum and facial nucleus believed to be involved in eye-head coordination and pinna movements. We did this by using the autoradiographic and horseradish peroxidase tracing techniques in 11 kittens, ranging in age from several hours to 14 days postnatal, and in seven adult cats. Even in the youngest animals studied, a dense projection was observed from the superior colliculus to each of the target structures examined. These included the parabigeminal nucleus, paralemniscal zone, dorsolateral pons, and inferior olive. Surprisingly, the only projection observed to undergo any postnatal maturational changes was the one to the paralemniscal zone (involved in the pinna-movement circuit of the superior colliculus), and the changes appeared as a reorganization of the terminal field rather than an increase in the density of transported label. Thus, no evidence was obtained to support our expectation that the superior colliculus efferents involved in orientation of the pinnae would develop earlier than those involved in visual orientation. Instead, each of the efferent projections of the superior colliculus examined in this study appears to be laid down prenatally and becomes adultlike long before functional maturity is reached. Presumably, then, the formation and elaboration of synaptic connections are the protracted postnatal processes that limit the functional properties of these neonatal efferent pathways.

Sources of subcortical projections to the superior colliculus in the cat.

A comprehensive search for subcortical projections to the cat superior colliculus was conducted using the retrograde horseradish peroxidase (HRP) method. Over 40 different subcortical structures project to the superior colliculus. The more notable among these are grouped under the following categories. Visual structures: ventral lateral geniculate nucleus, parabigeminal nucleus, pretectal area (nucleus of the optic tract, posterior pretectal nucleus, nuclei of the posterior commissure). Auditory structures: inferior colliculus (external and pericentral nuclei), dorsomedial periolivary nucleus, nuclei of the trapezoid body, ventral nucleus of the lateral lemniscus. Somatosensory structures: sensory trigeminal complex (all divisions, but mainly the gamma division of nucleus oralis), dorsal column nuclei (mostly cuneate nucleus), and the lateral cervical nucleus. Catecholamine nuclei: locus coeruleus, raphe dorsalis, and the parabrachial nuclei. Cerebellum: medial, interposed, and lateral nuclei, and the perihypoglossal nuclei. Reticular areas: zona incerta, substantia nigra, midbrain tegmentum, nucleus paragigantocellularis lateralis, and the hypothalamus. Evidence is presented that only the parabigeminal nucleus, the nucleus of the optic tract, and the posterior pretectal nucleus project to the superficial collicular layers (striatum griseum superficiale and stratum opticum), while all other afferents terminate in the deeper layers of the colliculus. Also presented is information concerning the rostrocaudal distribution of some of these afferent connections. These findings stress the multiplicity and diversity of inputs to the deeper collicular layers, and more specifically, identify multiple sources of the physiologically well-known representations of the somatic and auditory modalities in the colliculus.

Ventricular tachyarrhythmia due to cardiac sarcoidosis in a child.

Cardiac involvement by systemic sarcoidosis is well known, but occurs rarely. It usually manifests as either heart block, heart failure due to direct myocardial involvement, or cor pulmonale. We present the case of a patient with cardiac sarcoidosis who had ventricular tachycardia and congestive heart failure. Although there was other organ system involvement, the cardiac manifestation was the first to become clinically apparent. Therapy consisted of quinidine sulfate to control the arrhythmias and chronic diuretic therapy to control congestive heart failure. Steroid therapy was initially associated with recurrence of the ventricular tachycardia and was discontinued. It was reinstituted 18 months later when other organ system involvement developed with no recurrence of the ventricular tachyarrhythmia. The patient responded well to therapy and is currently doing well. This case is presented to illustrate a somewhat unusual, but nevertheless important, etiology of ventricular tachyarrhythmias. The recognition of underlying sarcoidosis is critical because of the propensity for other organ system involvement by this disease process.

Thoracoabdominal ectopia cordis with mosaic Turner's syndrome: Report of a case.

A child was treated for thoracoabdominal ectopia cordis and an associated chromosomal defect. Contrary to most cases in which death is due to the externally situated heart and abdominal viscera, this patient died from congenital heart disease.

Sodium channel abnormalities are infrequent in patients with long QT syndrome: identification of two novel SCN5A mutations.

Long QT syndrome (LQTS) is a heterogeneous disorder caused by mutations of at least five different loci. Three of these, LQT1, LQT2, and LQT5, encode potassium channel subunits. LQT3 encodes the cardiac-specific sodium channel, SCN5A. Previously reported LQTS-associated mutations of SCN5A include a recurring three amino acid deletion (DeltaKPQ1505-1507) in four different families, and four different missense mutations. We have examined the SCN5A gene in 88 index cases with LQTS, including four with Jervell and Lange-Nielsen syndrome and the remainder with Romano-Ward syndrome. Screening portions of DIII-DIV, where mutations have previously been found, showed that none of these patients has the three amino acid deletion, DeltaKPQ1505-1507, or the other four known mutations. We identified a novel missense mutation, T1645M, in the DIV; S4 voltage sensor immediately adjacent to the previously reported mutation R1644H. We also examined all of the additional pore-forming regions and voltage-sensing regions and discovered another novel mutation, T1304M, at the voltage-sensing region DIII; S4. Neither T1645M nor T1304M were seen in a panel of unaffected control individuals. Five of six T1304M gene carriers were symptomatic. In contrast to previous studies, QT(onset-c) was not a sensitive indicator of SCN5A-associated LQTS, at least in this family. These data suggest that mutations of SCN5A are responsible for only a small proportion of LQTS cases.

Corticotectal and other corticofugal projections in neonatal cat.

Adult physiological properties of cat superior colliculus cells develop gradually during the first two months of life. Since many of the neuronal properties in the adult cat appear to depend upon the integrity of visual cortex, it was postulated that the maturation of superior colliculus cells is, in large part, a reflection of corticotectal maturation. An attempt was made to study the development of the corticotectal pathway with the autoradiographic tracing technique. Injections of [3H]leucine were made in the visual cortex of kittens 6 h to 12 days of age and animals were sacrificed 20-24 h later. A dense projection from visual cortex to the superior colliculus and to the lateral geniculate nucleus was noted in all animals. Both projections appeared to be topographically organized. In addition, cortical projections to the lateral posterior-pulvinar region and sparse projections to the contralateral visual cortex were noted. Two, non-mutually exclusive, explanations for the presence of a corticotectal pathway in the absence of mature cell properties in the superior colliculus are most apparent: (a) corticotectal synapses are incompletely formed at birth and require many weeks to develop, and (b) corticotectal cells are immature during early postnatal life and cannot impress adult-like characteristics upon the superior colliculus cells until they, themselves, 'mature'.

Efferent projections of the neonatal superior colliculus: extraoculomotor-related brain stem structures.

The development of eye movements is a prolonged process which presumably involves the efferents of the superior colliculus. In the present study we sought to determine which, if any, of the colliculus efferents that influence eye movements in adult cats were present in neonatal kittens. The autoradiographic and orthograde horseradish peroxidase tracing methods were employed in kittens ranging from 6 h to 5 weeks of age and in adult cats. Surprisingly, most of the known projections from the superior colliculus which are believed to be involved in eye movements were already present in the youngest animals studied. These included projections to (a) the ventral central gray matter overlying the oculomotor nucleus, and (b) those portions of the pontine and medullary reticular formation which provide excitatory and inhibitory inputs to abducens neurons. Apparently, the pathways over which the superior colliculus influences eye movements are elaborated quite early in life. However, in the predorsal bundle and pontomedullary reticular areas the density of transported label was less in 1-day-old kittens than in older animals. Thus, anatomical as well as functional development of portions of this circuitry appear to require a significant period of postnatal maturation.

A comparison of the intranigral distribution of nigrotectal neurons labeled with horseradish peroxidase in the monkey, cat, and rat.

The location of neurons in the substantia nigra's pars reticulata (SNR) that send their axons to the superior colliculus was compared in the monkey, cat, and rat using the horseradish peroxidase (HRP) retrograde cell-labeling method. Although several cases of large, unilateral HRP deposits in the superior colliculus show that in all three species, the nigrotectal cells are confined, for the most part, to the rostral one-half of SNR, the following differences were noted in the precise location of the nigrotectal neurons and in the degree of bilaterality of the nigrotectal projection. In the monkey, labeled nigrotectal cells were particularly numerous in the extreme rostrolateral portion of SNR. From this region of high concentration, a progressively decreasing number of cells spreads medially in a ventral stratum immediately dorsal to the pes pedunculi. No labeled cells were found in the extreme medial part of SNR. A substantial number of HRP-positive cells were present in the contralateral SNR in a similar distribution. In the cat, labeled cells were less selectively localized in SNR's mediolateral expanse, being distributed more or less randomly in its middle portion with a scattering of cells in both medial and lateral parts of SNR. Although some cell labeling occurred in the contralateral SNR, it was less substantial than in the monkey. In the rat, the HRP-positive cells were especially concentrated throughout the mediolateral extent of a ventral stratum of SNR immediately dorsal to the pes pedunculi. Although some cells were located more dorsally, they were far fewer in number and consistently less heavily labeled. Only one or two labeled cells could be detected in the contralateral SNR of the rat. These anatomical differences suggest that the influence of the corpus striatum on the tectal control of orienting responses may vary considerably from one mammalian species to the next.