Faculty Bibliography

The activity of 43 antidromically identified abducens internuclear neurons with conduction velocities ranging from 14 to 54 m/s was analyzed in alert cats during spontaneous and vestibular induced eye movements. The discharge rate of internuclear neurons significantly increased with successive adducting positions of the contralateral eye. Slopes of rate-position (k) relationships ranged from 3.1 to 17.9 spikes/deg (mean 12.01 +/- 3.1). Threshold ranged from -19 degrees to +3 degrees. Frequency saturation was never observed for any internuclear neuron within the oculomotor range. Although straight lines were selected to illustrate the rate-position relationships, exponential curves always provided the best statistical fit demonstrating that an enhancement in frequency potentiation (k) must accompany more eccentric fixations in the on direction. Internuclear neurons showed a low variability in firing rate (less than 3.0%) for fixations less than 1 s. Variability increased with both longer and repeated fixations of the same eye position. Discharge rates were found to depend upon both the direction of the preceding eye movement and the animal's level of alertness. Separate regression lines of rate-position relations following saccades in the on and off directions differed significantly in slope (100%), but not threshold. The observed static hysteresis in an identified non-motoneuron shows this property to be in a central neural circuit prior to the extraocular motoneuron. The slopes (k) of rate-position plots for all internuclear neurons decreased significantly (100%) when level of alertness changed from "alert" (1 +/- 0.2 saccades/s) to "drowsy" (0.5 +/- 0.2 saccades/s). Thresholds, however, were not significantly altered. Discharge rate of abducens internuclear neurons increased abruptly 10.4 +/- 2.5 ms preceding saccades in the on direction, and decreased 20.5 +/- 7.8 ms before saccades in the off direction. Internuclear neuronal activity was not affected by pure vertical saccades. During on direction saccades, firing frequency did not saturate, but increased with velocity in a linear fashion. Exponential functions often fit the data better due to the difference in slopes of rate-velocity plots for on vs off direction saccades. Slopes (rs) of rate-velocity regression lines during spontaneous saccades ranged from 0.99 to 4.10 spikes/s/deg/s (mean 2.16 +/- 0.93). During saccades in the off direction activity always decreased, but it seldom ceased. Rate-velocity regression lines measured during the fast phase of vestibular nystagmus (rsv = 2.09 +/- 0.88) showed no significant differences from rs slopes in 82% of the cases.(ABSTRACT TRUNCATED AT 400 WORDS)

The efferent vestibular nuclei and nerves were studied in the toadfish, Opsanus tau, with morphological and electrophysiological techniques. The origin and course of the efferent vestibular nerves was extensively documented. One major morphological observation was that the efferent nerves comprise a peripheral network that is anatomically distinct, and separable by dissection from the primary afferents innervated by each end organ. These anatomically distinct nerves are likely to be a major asset in physiological studies of efferent vestibular function. The retrograde transport of horseradish peroxidase (HRP) from each of the nerves innervating the vestibular and lateral line organs was used to delineate the subgroups of efferent neurons projecting to these end organs. The efferent vestibular nuclei are located in the posterior medulla in and around the median longitudinal fasciculi (MLF). We divided the nuclei cytoarchitecturally into lateral, medial, and dorsal subdivisions. The lateral cells had bilateral dendritic trees while the dorsal cells had ipsilateral, unilateral dendritic trees. There was a higher proportion of lateral cells that innervated the canal organs and the utricle while the dorsal cells tended to innervate the other organs. The total number of cells obtained by summing those from separate nerve label was twice the total cell count present in the nuclei. Indirectly, this indicates that some cells project to more than one end organ. Efferent neurons were penetrated with glass microelectrodes, and their end organs and patterns of connectivity with other end organs were investigated by stimulating various vestibular nerves. Posterior semicircular canal efferent cells are electrically coupled to each other and could be activated electrically or chemically by stimulating other ipsilateral or contralateral vestibular nerves. It is suggested that electrical coupling might be responsible for the uniform behavior of these cells under certain conditions. Morphological and physiological experiments suggested that the semicircular canals are innervated by their own, exclusive populations of efferent neurons while other end organs may share efferent innervation. Single cells were injected intracellularly with HRP and their morphology was studied and characterized by light microscopy. Intracellular label confirmed the morphological features demonstrated by retrograde transport of HRP and also revealed that some cells had central axon collaterals that terminated within the MLF. These morphological and physiological results provide a basis for understanding the behavior of efferent vestibular neurons in the alert animal.

The peripheral and central oculomotor organization of the adult flatfish presents no morphological substrates that suffice to explain adaptive changes in its vestibuloocular reflex system. The necessity for an adaptation occurs because of a 90 degrees displacement of the vestibular with respect to the extraocular coordinate axes during metamorphosis. Since a reorganization of vestibuloocular pathways must be hypothesized (12), the location and termination of electrophysiologically identified secondary vestibular neurons with focus on the horizontal canal system was studied with the intracellular horseradish peroxidase method in adult winter flounders. Pseudopleuronectes americanus. The oculomotor target sites of vertical canal related neurons were similar to those described in mammals. Presumed excitatory anterior canal neurons bifurcated after the main axon had crossed the midline. The descending branch headed toward the spinal cord. The ascending branch reached the oculomotor nucleus via the contralateral medial longitudinal fasciculus and terminated in the superior rectus and inferior oblique subdivisions. Presumed inhibitory posterior canal neurons ascended ipsilaterally in the medial longitudinal fasciculus and terminated mainly in the superior rectus and inferior oblique subdivisions. Horizontal canal neurons exhibited characteristics distinctly different from mammalian ones. Two types of second-order neurons were observed. In the first case, cell bodies were located in the anterior portion of the vestibular nuclear complex. After crossing the midline, the axon ascended in the contralateral medial longitudinal fasciculus. Major termination sites were found in the inferior oblique and superior rectus subdivisions of the oculomotor nucleus. Axonal branches then recrossed the midline and terminated in identical locations on the ipsilateral side. In the second case, cell bodies were located in the descending vestibular nucleus. Their axons crossed the midline and also ascended in the contralateral medial longitudinal fasciculus. Major termination sites were in the trochlear nucleus and in the inferior rectus subdivision of the oculomotor nucleus. As in the first case, axonal branches also recrossed the midline and terminated in identical motoneuron pools on the ipsilateral side. The above target sites were exactly those expected to be used in a reciprocal excitatory-inhibitory fashion during compensatory eye movements. Head-down movement would be excitatory for the lower horizontal canal producing contractions of both superior recti and inferior obliques as well as relaxation of the antagonistic inferior recti and superior obliques.(ABSTRACT TRUNCATED AT 400 WORDS)

The flatfish species constitute a natural paradigm for investigating adaptive changes in the vertebrate central nervous system. During metamorphosis all species of flatfish experience a 90 degree change in orientation between their vestibular and extraocular coordinate axes. As a result, the optic axes of both eyes maintain their orientation with respect to earth horizontal, but the horizontal semicircular canals become oriented vertically. Since the flatfish propels its body with the same swimming movements when referenced to the body as a normal fish, the horizontal canals are exposed to identical accelerations, but in the flatfish these accelerations occur in a vertical plane. The appropriate compensatory eye movements are simultaneous rotations of both eyes forward or backward (i.e., parallel), in contrast to the symmetric eye movements in upright fish (i.e., one eye moves forward, the other backward). Therefore, changes in the extraocular muscle arrangement and/or the neuronal connectivity are required. This study describes the peripheral and central oculomotor organization in the adult winter flounder, Pseudopleuronectes americanus. At the level of the peripheral oculomotor apparatus, the sizes of the horizontal extraocular muscles (lateral and medial rectus) were considerably smaller than those of the vertical eye muscles, as quantified by fiber counts and area measurements of cross sections of individual muscles. However, the spatial orientations and the kinematic characteristics of all six extraocular muscles were not different from those described in comparable lateral-eyed animals. There were no detectable asymmetries between the left and the right eye. Central oculomotor organization was investigated by extracellular horseradish peroxidase injections into individual eye muscles. Commonly described distributions of extraocular motor neurons in the oculomotor, trochlear, and abducens nuclei were found. These motor neuron pools consisted of two contralateral (superior rectus and superior oblique) and four ipsilateral populations (inferior oblique, inferior rectus, medial rectus, and lateral rectus). The labeled cells formed distinct motor neuron populations, which overlapped little. As expected, the numbers of labeled motoneurons differed in horizontal and vertical eye movers. The numerical difference was especially prominent in comparing the abducens nucleus with one of the vertical recti subdivisions. Nevertheless, there was bilateral symmetry between the motoneurons projecting to the left and right eyes.(ABSTRACT TRUNCATED AT 400 WORDS)

Spinalized toadfish were held in a lucite chamber and perfused through the mouth with running seawater. Primary vestibular afferents and vestibular efferent axons and somas were studied with glass microelectrodes. Vestibular semicircular canal afferent and efferent axons were visually identified and penetrated with glass microelectrodes. Afferents responded to pulses of injected current with trains of action potentials, whereas efferents responded with only a single spike. This differential response to injected current served to further distinguish these two classes of nerve fibers that share the same canal nerve for part of their course. When current pulses were injected into efferent somadendritic recording sites, cells responded with trains of action potentials similar to those seen in other central nervous system neurons. Semicircular canal afferents were spontaneously active and occupied the same spectrum of regularity as vestibular afferents recorded in other species. Behavioral arousal evoked by lightly touching the fish on the snout or over the eye resembled spontaneous arousal observed in the field and consisted of eye withdrawal, fin erection, and attempted swimming. Efferent vestibular neurons were spontaneously active and increased their frequency of discharge when the fish was behaviorally aroused. Most efferents were briskly activated by behavioral arousal, but the time constant of the decay of their responses was variable ranging from 100 to 600 ms. Not only touch, but multimodal stimuli were capable of increasing the level of spontaneous activity of efferent vestibular neurons. The shortest latency to behavioral activation was 160 ms. Vestibular primary afferents also manifested increase in neuronal activity with behavioral activation. Irregularly discharging afferents were much more responsive than regularly discharging afferents. One rare case of transient inhibition in a regularly discharging afferent is illustrated. Severing the efferent vestibular nerve blocked behavioral activation in vestibular primary afferents. Electrical stimulation of the efferent vestibular nerve produced excitatory postsynaptic potentials (EPSPs) at latencies within the monosynaptic range in vestibular primary afferents. These monosynaptic EPSPs could produce action potentials in primary afferents or could sum with subthreshold depolarizations produced by current passed through the microelectrode to initiate impulses.(ABSTRACT TRUNCATED AT 400 WORDS)

The afferent and efferent connections of the nucleus prepositus hypoglossi with brainstem nuclei were studied using anterograde and retrograde axonal transport techniques, and by intracellular recordings and injections of horseradish peroxidase into prepositus hypoglossi neurons. The results of experiments in which horseradish peroxidase was injected into the prepositus hypoglossi suggest that the major inputs to the prepositus hypoglossi arise from the ipsi- and contralateral perihypoglossal nuclei (particularly the prepositus hypoglossi and intercalatus), vestibular nuclei (particularly the medial, inferior, and ventrolateral nuclei), the paramedian medullary and pontine reticular formation, and from the cerebellar cortex (flocculus, paraflocculus, and crus I; the nodulus was not available for study). Regions containing fewer labeled cells included the interstitial n. of Cajal, the rostral interstitial n. of the medial longitudinal fasciculus, the n. of the posterior commissure, the superior colliculus, the n. of the optic tract, the extraocular motor nuclei, the spinal trigeminal n., and the central cervical n. The efferent connections of the prepositus hypoglossi were studied by injecting 3H-leucine into the prepositus hypoglossi, and by following the axons of intracellularly injected prepositus hypoglossi neurons. The results suggest that in addition to the cerebellar cortex, the most important extrinsic targets of prepositus hypoglossi efferents are the vestibular nuclei (particularly the medial, inferior, and ventrolateral nuclei, and the area X), the inferior olive (contralateral dorsal cap of Kooy and ipsilateral subnucleus b of the medial accessory olive), the paramedian medullary and pontine reticular formation, the reticular formation surrounding the parabigeminal n., the contralateral superior colliculus and pretectum, the extraocular motor nuclei (particularly the contralateral abducens nucleus and the ipsilateral medial rectus subdivision of the oculomotor nucleus), the ventral lateral geniculate n., and the central lateral thalamic nucleus. Other areas which were lightly labeled in the autoradiographic experiments were the contralateral spinal trigeminal n., the n. raphe pontis, the Edinger Westphal n., the zona incerta, and the paracentral thalamic n. Many of the efferent connections of the prepositus hypoglossi appear to arise from principal prepositus hypoglossi neurons whose axons collateralize extensively in the brainstem. On the other hand, small prepositus hypoglossi neurons project to the inferior olive, and multidendritic neurons project to the cerebellar flocculus, apparently without collateralizing in the brainstem.(ABSTRACT TRUNCATED AT 400 WORDS)

The morphology of the neurons in the perihypoglossal nuclei (nucleus prepositus, nucleus intercalatus, and nucleus of Roller) of the cat was studied in normal Nissl material, and by intracellular injection of horseradish peroxidase. The neurons in the nucleus prepositus were morphologically heterogeneous. Many of the cells in the ventromedial part of the caudal prepositus had relatively large somata, and complex dendritic trees which arose from numerous proximal dendrites and ramified extensively in the ventromedial aspect of the prepositus. These neurons had thick axons which typically did not give rise to local collaterals. The cells in the dorsolateral part of the caudal prepositus tended to have small somata, and dendritic trees which arborized in that region of the nucleus. The axons of these small cells frequently gave rise to local collaterals which terminated in the prepositus. Most of the cells in the prepositus had medium-sized somata and relatively few dendrites which branched in an isodendritic manner and extended for long distances, frequently leaving the nucleus. These "principal" prepositus neurons had axons which arborized unilaterally, and often gave rise to collaterals which terminated in either the ipsilateral or contralateral prepositus. The neurons in the nucleus of Roller and nucleus intercalatus which were intracellularly injected with horseradish peroxidase resembled the multidendritic and small prepositus cells, respectively. The intrinsic connectivity of the perihypoglossal nuclei was also studied by injecting horseradish peroxidase or 3H-leucine into the prepositus nucleus. The results of these experiments suggest that the perihypoglossal nuclei are highly interconnected bilaterally, although the large cells in the ventromedial prepositus and the nucleus of Roller contribute little to these intrinsic connections, and are not major recipients of intrinsic inputs. On the other hand, the magnitude of the reciprocal connections between the prepositus and the nucleus intercalatus suggests that they are functionally related.

Retrograde tracing with horseradish peroxidase showed that motoneurons to two distinct muscles, the orbicularis oculis and quadratus labii superioris, are intermixed within the dorsolateral subnucleus of the cat facial nucleus. Intracellular electrodes were used to identify and fill the motoneurons of the dorsolateral subnucleus with horseradish peroxidase. Soma diameters averaged 55 micron. The average number of primary dendrites was 11.6. The area covered by the dendritic trees varied in shape according to the position of the soma within the subnucleus. Axon hillocks were seen arising in many orientations, bearing no apparent relation to subsequent axonal path, cell position within the nucleus or somatic geometry. Motoneurons to the two muscles appeared to be indistinguishable on the basis of morphology, even though they appear to be functionally independent. Their functional differences are not reflected in any measure of somadendritic shape studied here. Of further interest is the variability in shape associated with the neurons's position within the subnucleus. We conclude that many details of dendritic shape do not reflect specific physiological function.