Faculty Bibliography

1. The vestibulo-ocular reflex, a sensorimotor process, operates in a similar manner for homeothermic (mammals) and poikilothermic (fish) animals. However, individual physiological, biochemical, and/or pharmacological thermolabile processes that underlie the operation of this reflex could alter the operation of this reflex in a poikilotherm. The object of this study was to determine what aspects of the vestibulo-ocular reflex are affected by temperature changes naturally experienced by a poikilothermic animal, the goldfish. 2. Experiments were conducted on the visuovestibulo-(Vis-VOR) and vestibulo-ocular reflex (VOR) during normal operation as well as during the acquisition (learning) and retention (memory) phases of adaptive gain change. These studies were carried out at temperatures to which goldfish had been acclimated over several weeks and after rapid (< 5 min) shifts from this acclimation temperature. 3. Normal sinusoidal Vis-VOR and VOR gains before adaptation were found to be independent of the acclimation temperature over a wide range. Acute temperature changes of up to 10 degrees C either above or below a 20 degrees C acclimation temperature (Ac degree C = 20 degrees C) did not significantly modify normal visual and/or vestibular oculomotor reflex gains. 4. Surprisingly, slight reductions in temperature, as small as 2.5 degrees C, noticeably reduced Vis-VOR and VOR gain adaptations. Both short (3 h) and intermediate (up to 48 h) term reflex modifications were affected. Loss of adaptation was observed 10 degrees C below the acclimation temperature (Ac - 10 degrees C); however, return to the original temperature immediately restored most (60-100%) of the previously acquired Vis-VOR and VOR gain changes. In contrast, elevation of temperature up to 10 degrees C above the acclimation temperature (Ac + 10 degrees C) did not alter either increases or decreases in the adapted Vis-VOR or VOR gain. 5. A decrease in temperature reduced the magnitude of an adapted VOR gain increase and elevated the magnitude of an adapted gain decrease, thus returning the VOR gain back toward its normal control gain before adaptation. Because both increases and decreases in VOR gain were affected by the same temperature reduction, the cold effect was not a generalized reflex suppression, but inactivation of a process responsible for maintaining VOR adaptation. 6. During the acquisition phase, the time course and magnitude of adaptive VOR gain increases at temperatures acutely set 8-10 degrees C below the acclimation temperature were similar to those obtained at the acclimation temperature. Because the same temperature decrease inactivated retention of adapted VOR gain changes, the neuronal processes underlying the acquisition and the retention phases of Vis-VOR or VOR adaptation are suggested to differ qualitatively. 7. With the use of velocity step stimuli, both the adapted dynamic (< 100 ms) and sustained (> 100 ms) components of VOR adaptation were reduced by cooling. This effect on the dynamic component demonstrates an alteration in the shortest latency pathway through the vestibular nucleus and indicates that one thermosensitive site resides in the brain stem. 8. These results also show that, over a wide range of temperatures (20 +/- 10 degrees C), the neuronal processing that is responsible for the normal operation of the visuovestibulo- and/or vestibulo-ocular reflex and for the retention of reflex adaptation functions by separate physiological processes within the same brain stem and cerebellar circuitry. 9. We conclude that temperature exhibits a unique, and unexpected, state-dependent effect on sensorimotor regulation and adaptation for periods up to 48 h. Temperature does not alter normal VOR or the acquisition phase of an adapted gain change. (ABSTRACT TRUNCATED)

The developmental relations between abducens (VI) nerves and their targets, the lateral rectus, quadratus, and pyramidalis muscles, have been examined in the chick embryo from early neural tube stages through 10 days of incubation. Sites of myoblast origins were determined by microinjection of replication-incompetent retroviruses containing the LacZ reporter into paraxial mesoderm corresponding to somitomeres 3-5. Motor neurons and axons were identified by Bodian staining, immunocytochemistry, and application of DiI and DiO to dissected peripheral nerves. Anlage of the dorsal oblique originate in somitomere 3, close to the ventrolateral margin of the mid-to-caudal mesencephalon. Precursors of the lateral rectus arise deep within somitomere 4, beside the future metencephalon (rhombomere "A"). Quadratus and pyramidalis precursors are located between and partially segregated from these other two anlage. VIth nerve axons exit rhombomeres 5 and 6 via multiple median roots, fasciculate, and by stage 17 have elongated rostrally beneath the hindbrain. Immediately caudal to a mesenchymal pre-muscle condensation located deep to rhombomere 2, the VIth nerve separates into two branches. One branch enters the rostral portion of the condensation, from which quadratus and pyramidalis muscles will segregate. This branch projects exclusively from rhombomere 5 and is the accessory abducens nerve. The other branch enters the caudal, presumptive lateral rectus, region of the condensation. This is the abducens nerve, and it projects from cells located in both rhombomeres 5 and 6. These findings indicate that specific matching of motor nerves with their presumptive targets begins prior to the differentiation and segregation of myogenic populations, and that spatial organization of developing eye muscles is initiated well before they interact with connective tissue precursors derived from the neural crest.

1. The time course of eye velocity responses elicited by head velocity steps was compared in normal, adapted, and cerebellectomized goldfish. Vestibuloocular reflex (VOR) adaptation was induced by combined visual and vestibular stimulation that altered the ratio of eye to head velocity (VOR gain) toward values either higher or lower than the control amplitude. The velocity step consisted of alternating periods of head rotation at a constant velocity of 16 degrees/s zero-to-peak around the vertical axis. 2. The VOR produced by head velocity steps consisted of an early acceleration-related component, the dynamic response, separated from a sustained period of constant velocity, the plateau, by a sag that occurred around 125-150 ms. Latency of the VOR averaged 18 ms for the adducting eye and 20 ms for abducting eye independent of the initial VOR gain. Adapted dynamic VOR responses diverged from the control records at the earliest detectable latency after both high and low VOR gain training. This result demonstrates modification in the shortest latency brain stem VOR pathway, presumably, the three-neuron reflex arc. 3. After acute cerebellectomy the adapted dynamic response was unaltered for approximately 50 ms in the low-gain and 70 ms in the high-gain VOR states. Not less than 30% of the altered velocity was retained throughout the remaining dynamic and sustained component. These results demonstrate that the vestibulocerebellum is not necessary for the maintenance of the earliest adapted eye velocity. Hence brain stem pathways are sufficient for the expression of the modified VOR. 4. Purkinje cells identified by simple and complex spikes were recorded extracellularly in the area of the vestibulocerebellum, where electrical stimulation produced conjugate ipsiversive horizontal eye movements. Independent eye and head velocity sensitivities were determined in response to visual world motion and VOR suppression, respectively. The two signals either added, canceled, or were both present in Purkinje cells throughout the range of eye velocity induced by vertical axis visual-vestibular stimulation. 5. Latency of Purkinje cell discharge to either a vestibular or visual velocity step exhibited means of 43 and 70 ms, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Many teleost fish generate acoustic signals for vocal communication by the synchronized, high-frequency contraction of skeletal, sonic muscles. In midshipman, eight groups of brainstem neurons were distinguished after biocytin application to the sonic nerve that, we propose, represent the entire vocal motor circuit. Biocytin-filled terminals were ubiquitous within all areas containing labeled neurons and, together with ultrastructural evidence, suggested a serial, transneuronal transport at synaptic sites between at least three neuronal groups. The most intensely labeled neurons were positioned in the caudal brainstem and included a previously characterized pacemaker-motoneuron circuit and a newly recognized ventral medullary nucleus that itself gave rise to extensive commissural and lateral brainstem bundles linking the pacemaker circuitry to the rostral brainstem. Five additional groups formed a column rostrally within the medial brainstem adjacent to eighth nerve (octaval)-recipient nuclei largely presumed to be acoustic. This column extended dorsally up to the ventricular cell layer and as far anterior as midbrain isthmal levels. The best-defined group was in the octaval efferent nucleus that directly innervates the sacculus that is considered the auditory division of the inner ear. Saccular afferents and neurons throughout the medial column were also filled after biocytin application to the saccular nerve. This vocal-acoustic network overlaps low-threshold, electrical stimulation sites in the rostral brainstem that elicit vocalizations. The medial column must therefore be the origin of the descending pathway controlling activation of the vocal pacemaker circuitry and likely forms the basis for acoustically elicited vocalizations. We suggest this network, together with input from the pacemaker circuitry, is also the origin of a vocal-related, corollary discharge to acoustic nuclei. Direct links between vocal and acoustic brain regions are thus traits common to aquatic and terrestrial vertebrates.

Two types of central nervous system integrators are critical for oculomotor performance. The first integrates velocity commands to create position signals that hold fixation of the eye. The second stores relative velocity of the head and visual surround to stabilize gaze both during and after the occurrence of continuous self and world motion. We have used recordings from single neurons to establish that the "position" and "velocity" integrators for horizontal eye movement occupy adjacent, but nonoverlapping, locations in the goldfish medulla. Lidocaine inactivation of each integrator results in the eye movement deficits expected if horizontal eye position and velocity signals are processed separately. These observations also indicate that each brainstem compartment generates and stores these signals. Consequently, each integrator exhibits functional autonomy. Therefore, we propose that the intrinsic electrophysiological properties of the constituent neurons in each brainstem subnucleus may be sufficient for producing integrator rhythmicity.

The organization of embryonic efferent cranial nerves is addressed here by interspecies comparison of segmentally patterned neuromeres, efferent neuronal populations and early mesodermal sources of target muscles. The segmental constancy of these three structural patterns is evaluated for elasmobranch, teleost, reptile, bird and mammal embryos and compared with the segmentally restricted expression patterns of Hox genes. A conserved series of hindbrain neuroepithelial segments (rhombomeres) is present in all of these taxa. Dye-labeling experiments demonstrate that the segmental locations of efferent neurons projecting through individual cranial nerves are likewise highly conserved. Notable segmental variation is however shown in the location of the VI and IX-XII motoneurons, suggesting the likelihood of homeotic-like changes in relations between rhombomere and neuronal 'identity' during vertebrate evolution. Since experimentally induced shifts in expression borders of Hox genes appear to be correlated with alterations in segment identity and/or neuronal phenotype, the need for further examination of segmental locations of specific neuronal groups and the segmental expression patterns of Hox genes between species is emphasized. Comparison of early cranial mesodermal subdivisions in elasmobranchs with descriptions of somitomeres in amniotes suggests that a series of axially unique mesodermal populations may also be conserved throughout vertebrates. The possibility is raised that common mechanisms of axial specification may underlie the initial appearance of segmental patterning in both neural and mesodermal layers during gastrulation. Implications of these conserved patterns for understanding the phylogenetic origin of the vertebrate head are briefly discussed

1. The normal and adapted vestibuloocular reflex (VOR) of goldfish was characterized by means of sinusoidal, velocity step, and position step head rotations about the vertical axis. VOR adaptation was induced by short-term, 1- to 4-h, presentation of visual and vestibular stimuli that altered the ratio of eye to head velocity. 2. The VOR response measured with sinusoidal oscillations in the dark was close to ideal compensatory values over 2 decades (1/32-2 Hz). Gain approximated unity, and phase, in relation to the head, was nearly 180 degrees. The VOR was linear within the range of head velocity tested (4-64 degrees/s). 3. Head velocity steps from 1/8 to 1 Hz produced steplike eye velocity profiles that could be divided into an early acceleration-related 'dynamic' component and a later constant-velocity 'sustained' period frequently separated by a sag at approximately 0.1-0.15 s from the initiation of eye movement. The sustained response exhibited no decay during the constant-velocity component of the step. 4. Higher temporal resolution of the dynamic response showed the adducting eye movement to have a shorter latency, faster rise time, and larger peak gain than the abducting eye movement. The characteristics of this directional asymmetry were similar for position steps and electrical stimulation of the vestibular nerve. However, the asymmetry was not observed during sinusoidal head rotation, the sustained component of the step response, or after electrical stimulation of the VIth and IIIrd nerves. We conclude that this directional asymmetry is of central origin and may be largely due to the parallel vestibular and abducens internuclear neuron pathways onto medial rectus motoneurons. 5. The VOR adaptation process for both higher and lower eye velocity exhibited an exponential time course with time constants of 55 and 45 min, respectively. After continuous sinusoidal training for 4 h, VOR gain reached an asymptotic level 5% away from perfect suppression in the low-gain training, but 19% away from the actual performance in the high-gain paradigm. The time constant for VOR gain reversal was 5 h, and an asymptotic level 40% less than performance was reached within 10 h. 6. Adapted VOR gain was symmetrical for both directions of eye movement measured either during sinusoidal rotation or the sustained part of the velocity step. VOR adaptation also produced a comparable gain change in the nasal and temporal directions of the dynamic component, but this reflected the asymmetric characteristics observed in the preadapted condition.(ABSTRACT TRUNCATED AT 400 WORDS)

Anatomical studies were undertaken to analyze the brainstem organization of the auditory, vestibular, and lateral line nuclei in a teleost, the oyster toadfish, Opsanus tau. Neuronal cytoarchitectonics and horseradish peroxidase label of cranial nerves were utilized to delineate the borders of the five octavus and two lateralis brainstem nuclei. Each of the eight octavolateralis nerves were labeled individually to compare and contrast their central projections. Projections of the three semicircular canals were found to be largely overlapping. Terminal fields were observed within the eminentia granularis and in each of the octavus nuclei. The nucleus anterior octavus was reciprocally innervated by the semicircular canals and the saccule. The canals terminated heavily in the ventral portions of the anterior octavus, whereas the saccule terminated extensively in the dorsal nuclear portions. The saccule also distributed terminals throughout the octavus cell column, including a light terminal field within the dorsal, medial, and anterior portions of the descending octavus nucleus, a region densely innervated by this end-organ in other species. These results suggest that the anterior octavus nucleus may have a dual function. The dorsal portions may be an auditory relay nucleus, whereas the ventral portions may subserve vestibular function. Utriclar and lagenar afferents also terminated throughout the octavus cell column. Afferents of the anterior and posterior lateral lines ended within the eminentia granularis and the lateral line nuclei. Semicircular canal afferents and lateral line afferents appeared completely segregated within the eminentia. The above results are useful as an aid in the understanding of an ongoing, comprehensive functional analysis of auditory and vestibular mechanisms in toadfish and complement previous work on the efferent vestibular and sound-producing motor systems. Examination of toadfish contributes to a more general and complete overview of the octavolateralis area of teleosts and the eventual identification of primitive and derived patterns of octaval organization. Additionally, this work may permit the further demonstration of species-typical characters that may indicate adaptations to particular behavioral repertoires.