Horizontal eye movement networks in primates as revealed by retrograde transneuronal transfer of rabies virus: differences in monosynaptic input to "slow" and "fast" abducens motoneurons.

The sources of monosynaptic input to "fast" and "slow" abducens motoneurons (MNs) were revealed in primates by retrograde transneuronal tracing with rabies virus after injection either into the distal or central portions of the lateral rectus (LR) muscle, containing, respectively, "en grappe" endplates innervating slow muscle fibers or "en plaque" motor endplates innervating fast fibers. Rabies uptake involved exclusively motor endplates within the injected portion of the muscle. At 2.5 days after injections, remarkable differences of innervation of slow and fast MNs were demonstrated. Premotor connectivity of slow MNs, revealed here for the first time, involves mainly the supraoculomotor area, central mesencephalic reticular formation, and portions of medial vestibular and prepositus hypoglossi nuclei carrying eye position and smooth pursuit signals. Results suggest that slow MNs are involved exclusively in slow eye movements (vergence and possibly smooth pursuit), muscle length stabilization and gaze holding (fixation), and rule out their participation in fast eye movements (saccades, vestibulo-ocular reflex). By contrast, all known monosynaptic pathways to LR MNs innervate fast MNs, showing their participation in the entire horizontal eye movements repertoire. Hitherto unknown monosynaptic connections were also revealed, such as those derived from the central mesencephalic reticular formation and vertical eye movements pathways (Y group, interstitial nucleus of Cajal, rostral interstitial nucleus of the medial longitudinal fasciculus). The different connectivity of fast and slow MNs parallel differences in properties of muscle fibers that they innervate, suggesting that muscle fibers properties, rather than being self-determined, are the result of differences of their premotor innervation.

Density gradients of trans-synaptically labeled collicular neurons after injections of rabies virus in the lateral rectus muscle of the rhesus monkey.

We evaluated the two-dimensional distribution of superior colliculus (SC) neurons visualized after retrograde transneuronal transport of rabies virus injected into the lateral rectus muscle of rhesus monkeys to test whether the density of projection neurons might play a role in the spatiotemporal transformation and vector decomposition. If this were the case, the number of horizontal eye movement-related SC neurons should increase with their distance from the rostral pole of the SC and decrease with their distance from the representation of the horizontal meridian. Labeled neurons of the intermediate SC layers were counted inside a 1-mm-wide band that matched the horizontal meridian of the collicular motor map. Local areal densities were plotted against distance from the rostral SC pole. At 2.5 days after inoculation, there was no labeling in the SC. At 3 days, moderate labeling appeared on both sides, mostly in the intermediate layers. At 3.5 days, cell numbers substantially increased and the laminar distribution changed as cells appeared in the superficial SC layers. At 3 days, rostrocaudal density profiles were unimodal, with peaks at locations near 50 degrees (contralateral SC) and 25-30 degrees (ipsilateral SC) horizontal eccentricity. At 3.5 days, distributions were bimodal due to the appearance of a second high-density region near the rostral pole of the SC. The distribution of SC neurons influencing the abducens nucleus, thus, was nonuniform. Caudal sites contained more neurons, but the experimentally observed density gradients were shallower than the theoretically predicted ones that would be necessary to fully account for the spatiotemporal transformation. Similarly, we studied the distributions of cell densities in the intermediate SC layers along an isoamplitude line (representing saccades of equal amplitudes but different directions). Consistent with theoretical estimates of the density gradients required for vector decomposition, we found that the concentrations of labeled cells were highest in the vicinity of the horizontal meridian but their decrease toward the periphery of the motor map was steeper than predicted. We conclude that SC cell density gradients cannot fully account for the spatiotemporal transformation and vector decomposition in the absence of an additional mechanism such as the previously demonstrated (Grantyn et al., [1997] Soc. Neurosci. Abstr. 23:1295; Moschovakis et al., [1998] J. Neurosci. 18:10219-10229) locus-dependent weighting of the strength of efferent projections to the saccade generators.

Direct projections of omnipause neurons to reticulospinal neurons: a double-labeling light microscopic study in the cat.

Omnipause neurons (OPNs) are inhibitory neurons located in the midline region of the caudal pons. Their role in gating the discharges of saccade-related burst neurons is well known, but there is no agreement concerning their influence on brainstem neurons that control other muscle groups participating in rapid gaze shifts. In the present study, we inquired whether OPNs project directly to pontobulbar reticulospinal neurons (RSNs) in the cat. Retrograde transport of horseradish peroxidase from the cervical spinal cord was used to label RSNs and an anterograde tracer (biocytin) was iontophoresed at sites of extracellular recording of the OPN activity. Somadendritic characteristics of biocytin-labeled OPNs were largely similar to those obtained previously with intracellular labeling. Three-dimensional reconstruction of axonal trajectories and collaterals revealed that projections of OPNs, regarded as a population, are bilateral. Their terminals were restricted to the reticular formation and midline structures throughout the rostral bulbar and pontine tegmentum. Appositions of synaptic boutons originating from five fully stained OPNs were detected on 38 retrogradely labeled RSNs, each of the OPNs contacting 3-13 cells. The numbers of boutons (1-46; mean 11.8) on the RSN somata and proximal dendrites indicate that the anatomical strength of paired OPN-RSN connections is comparable to that of other similarly studied inhibitory neurons in the cat. The existence of connections with RSNs supports the hypothesis of a generalized influence of OPNs on several effectors participating in orienting gaze shifts as opposed to the idea of their strict specialization for the control of eye saccades.