Alexej Grantyn

The control of slow orienting eye movements by tectoreticulospinal neurons in the cat: behavior, discharge patterns and underlying connections.

The activity of tectoreticulospinal neurons (TRSN) during orienting gaze shifts was studied in alert, head-fixed cats by intra-axonal recordings. The scope of the study was to evaluate the role of this class of superior colliculus neurons in the generation of slow eye movements (drifts) which often follow main-sequence saccades and sometimes appear as an independent motor event of orienting. The parameters of such movements are described in the first part of the paper. The organization of underlying pathways in the lower brainstem has been studied by intra-axonal horseradish peroxidase (HRP) tracing. The mean amplitude of postsaccadic drifts (PSD) is 1.21° (SD 0.63), but it can eventually reach 6–8°. PSDs have mean velocity of 14.9°/s (SD 4.28) and mean duration of 104.2 ms (SD 50.8). These two parameters are positively correlated with PSD amplitude. The presence of PSDs is usually associated with an increased neck muscle activity on the side toward which the eyes move. The durations of these two motor events show a reliable positive correlation. PSDs appear to occur when gaze error persists after a saccade and a correction is attempted by means of a slow eye movement and a head turn. The durations of TRSN bursts are, on average, longer than the sum of the lead time and the saccade duration. Bursts associated with combinations of saccades and PSD are significantly longer than those recorded in the absence of PSDs. The probability of occurrence of PSDs is higher when firing of TRSNs continues after saccade termination. Such prolonged discharges usually coincide with a combination of PSDs and phasic activation of the neck electromyogram. The mean firing rate of TRSNs during PSDs is 62% of that during saccade-related portions of the burst and declines to 45% after the end of PSDs. According to its timing and intensity, postsaccadic firing of TRSNs is appropriate as a signal underlying slow, corrective eye movements and later portions of phasic neck muscle contractions during orienting. Intraaxonal HRP labeling showed that visuomotor TRSNs of the X type (n = 3) terminate in the abducens nucleus, with 145–331 boutons terminaux and en passant. Average bouton densities in the nucleus are lower than in the periabducens reticular formation, but higher than in more rostral paramedian pontine reticular formation (PPRF) regions. Terminal fields in the PPRF match the locations of “eye-neck” reticulospinal neurons (RSNs) and exitatory burst neurons. Termination densities comparable with those in the caudal PPRF are found also in the rostral nucleus reticularis gigantocellularis, which contains phasic RSNs (“neck bursters”) and inhibitory burst neurons. Morphological observations alone do not exclude firing rate modulation of abducens motoneurons through the monosynaptic tectal pathway. However, the available physiological data point to a major role of a multiple convergent connection involving the eye-neck RSNs. In conclusion, the signals of X type TRSNs, reinforced by parallel connection through RSNs, encode mainly the intended head movement. Collateral actions of these two populations may be sufficient to induce slow, orienting eye movements, independently of the burst output from the classic saccadic generator.

Neuronal mechanisms of two-dimensional orienting movements in the cat. I. A quantitative study of saccades and slow drifts produced in response to the electrical stimulation of the superior colliculus

To evaluate the metrics of rapid eye movements caused by the activation of distinct collicular microzones, the superior colliculus (SC) was electrically stimulated in alert behaving cats while their heads were restrained. A quantitative study of electrically induced rapid eye movements demonstrated that their amplitude and direction depended on the intensity of stimulation, the electrode location, and the initial position of the eyes, while their duration depended on the intensity of stimulation. When detailed quantitative procedures are employed, properties of saccades produced in response to the electrical stimulation of the feline SC resemble those of saccades elicited in response to the electrical stimulation of a variety of primate brain areas. Besides saccades, electrical stimulation of the feline SC gave rise to slow drifts whose amplitude and direction was also influenced by the initial position of the eyes. Because their size depended on the frequency of stimulation and their time course reflected mechanical properties of the oculomotor plant, induced slow drifts could be due to a more or less direct projection of the SC onto extraocular motoneurons. A model that includes such a variety of connections between the SC and extraocular motoneurons is presented and is shown to produce realistic combinations of fast and slow eye movements when its input is a step function of time. The present findings support the notion that an orbital mechanical factor underlies the eye position sensitivity of slow drifts and saccades evoked in response to the electrical stimulation of the SC.

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. J. Comp. Neurol. 451:346–361, 2002.

Saccades and multisaccadic gaze shifts are gated by different pontine omnipause neurons in head-fixed cats

Abstract Pontine omnipause neurons (OPNs) have so far been considered as forming a homogeneous group of neurons whose tonic firing stops during the duration of saccades, when the head is immobilized. In cats, they pause for the total duration of gaze shifts, when the head is free to move. In the present study, carried out on alert cats with fixed heads, we present observations made during self-initiated saccades and during tracking of a moving target which show that the OPN population is not homogeneous. Of the 76 OPNs we identified, 39 were found to have characteristics similar to those of previously described neurons, ”saccade” (S-) OPNs: (1) the durations of their pauses were significantly correlated with the durations of saccades; (2) the discharge ceased shortly before saccade onset and resumed before saccade end; (3) visual responses to target motion were excitatory; and (4) during tracking, S-OPNs interrupted the discharge for the duration of saccades and resumed firing during perisaccadic ”drifts”. However, the characteristics of 37 neurons (”complex” (C-) OPNs) were different: (1) the pause duration was not correlated with the duration of self-initiated saccades; (2) time lead of pause onsets relative to saccades was, on average, longer than in the group of S-OPNs, and firing resumed after the saccade end; (3) visual target motion suppressed tonic discharges; and (4) during tracking, firing was interrupted for the total duration of gaze shifts, including not only saccades but also perisaccadic ”drifts”. We conclude that cat OPNs can be subdivided into two main groups. The first comprises neurons whose firing patterns are compatible with gating individual saccades (”saccade” OPNs). The second group consists of ”complex” OPNs whose firing characteristics are appropriate to gate total gaze displacements rather than individual saccades. The function of these neurons may be to disinhibit pontobulbar circuits participating in the generation of saccade sequences and associated perisaccadic drifts.

Control of orienting movements: role of multiple tectal projections to the lower brainstem

In movement neuroscience this past decade, a conceptual approach that puts emphasis on population coding was clearly dominant. The purpose of numerous studies has been to define presumably homogeneous groups of neurons on the basis of the correlation of their discharges with sensory and motor events. The goal of this chapter is to stress the importance of taking into account individual properties of neurons, this being an essential prerequisite for a biologically meaningful definition of neuron populations. Taking as an example the executive limb of the neural network controlling gaze movements, we demonstrate the functional and anatomical diversity of tectal and reticular neurons, which are generally considered as homogeneous populations and used, accordingly, as lumped elements in models. We argue that the extraction of effector-specific signals from the global command of gaze displacement is based not on the interplay between discrete neural modules, but rather on a gradual process of signal specification at all levels of the executive network. An eventual accurate description of this network will require knowledge of the unique combinations of afferent inputs and efferent connections for as many subsets of its constituent neurons as is conceivably possible.

Tracing premotor brain stem networks of orienting movements

Methods allowing a direct matching of movement-related firing patterns and connectivity of individual neurons have been used in the analysis of premotor networks controlling orienting movements. Advances have been made in the description of coding properties of orienting-related tectal output neurons, as well as in specifying their distributed connections in the brain stem and possible modes of coupling to saccadic pattern generators in the reticular formation. New data on the properties of signals and connectivity patterns have also been obtained for the tecto-recipient reticulo-spinal neurons. At least a small portion of the network performing the spatio-temporal transformations of orienting-related tectal efferent signals can now be described both in functional and in morphological terms.

The local loop of the saccadic system closes downstream of the superior colliculus

Models of the saccadic system differ in several respects including the signals fed back to their comparators, as well as the location and identity of the units that could serve as comparators. Some models place the comparator in the superior colliculus while others assign this role to the reticular formation. To test the plausibility of reticular models we stimulated electrically efferent fibers of the superior colliculus (SC) of alert cats along their course through the pons, in the predorsal bundle (PDB). Our data demonstrate that electrical stimulation of the PDB evokes saccades, even with stimuli of relatively low frequency (100 Hz), which are often accompanied by slow drifts. The velocity and latency of saccades are influenced by the intensity and frequency of stimulation while their amplitude depends on the intensity of stimulation and the initial position of the eyes. The dynamics of evoked saccades are comparable to those of natural, self-generated saccades of the cat and to those evoked in response to the electrical stimulation of the SC. We also show that PDB-evoked saccades are not abolished by lesions of the SC and that therefore antidromic activation of the SC is not needed for their generation. Our data clearly demonstrate that the burst generator of the horizontal saccadic system is located downstream of the SC. If it is configured as a local loop controller, as assumed by most models of the saccadic system, our data also demonstrate that its comparator is located beyond the decussation of SC efferent fibers, in the pons.

Anatomical evidence for ipsilateral collicular projections to the spinal cord in the cat

Injections of WGA-HRP were made within the C1 segment of spinal cord in cats with a midsagittal section of the midbrain. A small number of labelled cells were found in the latero-caudal part of the deeper layers of the superior colliclus (SC) ipsilateral to the injection sites. Because of the complete section of the dorsal tegmental decussation, these results definitively demonstrate the existence of an ipsilateral tecto-spinal pathway projecting to upper cervical segments in the cat. Ipsilaterally projecting tecto-reticulo-spinal neurons represent about 5% of the total population of tectospinal neurons. They were exclusively located in the deeper collicular layers and most of them were found in the latero-caudal part of the SC. Comparison with our previous studies suggests that more ipsilateral tectospinal projections that found after the section of the dorsal tegmental decussation probably exist. They may arise from tecto-reticulo-spinal neurons recrossing the midline in the brainstem or in the rostral part of C1. By analogy with the cortico-spinal tract, we suggest that the existence of an ipsilateral tecto-spinal pathway can be regarded as evidence for a substantial development of the cat tecto-spinal system as compared with other mammals.

Asymmetrical Interhemispheric Connections Develop in Cat Visual Cortex after Early Unilateral Convergent Strabismus: Anatomy, Physiology, and Mechanisms

In the mammalian primary visual cortex, the corpus callosum contributes to the unification of the visual hemifields that project to the two hemispheres. Its development depends on visual experience. When this is abnormal, callosal connections must undergo dramatic anatomical and physiological changes. However, data concerning these changes are sparse and incomplete. Thus, little is known about the impact of abnormal postnatal visual experience on the development of callosal connections and their role in unifying representation of the two hemifields. Here, the effects of early unilateral convergent strabismus (a model of abnormal visual experience) were fully characterized with respect to the development of the callosal connections in cat visual cortex, an experimental model for humans. Electrophysiological responses and 3D reconstruction of single callosal axons show that abnormally asymmetrical callosal connections develop after unilateral convergent strabismus, resulting from an extension of axonal branches of specific orders in the hemisphere ipsilateral to the deviated eye and a decreased number of nodes and terminals in the other (ipsilateral to the non-deviated eye). Furthermore this asymmetrical organization prevents the establishment of a unifying representation of the two visual hemifields. As a general rule, we suggest that crossed and uncrossed retino-geniculo-cortical pathways contribute successively to the development of the callosal maps in visual cortex.

Post-spike facilitation of neck EMG by cat tectoreticulospinal neurones during orienting movements.

1. The activity of fourteen tectoreticulospinal neurones (TRSNs) was recorded intraaxonally in the caudal pons of alert cats during orienting movements towards visual stimuli. TRSN spikes were used to compute the spike‐triggered average (STA) of rectified EMG of dorsal neck muscles. 2. Eight TRSNs for which 400‐2532 spikes were available were analysed with the STA technique. When the STA was computed from all spikes, significant post‐spike facilitation (PSF) was obtained for six of eighteen cell‐muscle pairs investigated (5 TRSNs). The mean relative amplitude of PSFs was 7.4% (S.D. 3.7). The onset latencies ranged from 1.1 to 5.0 ms and mean duration was 11.4 +/‐ 3.1 ms (mean +/‐ S.D.). 3. Interspike interval distributions were unimodal, with modes between 2.7 and 12.7 ms. Spike trains of TRSNs that produced significant PSFs contained 5‐13% of the interspike intervals < or = 5 ms and 22‐37% of the intervals < or = 10 ms. To evaluate the contribution of short intervals to PSF, STAs were computed separately for spikes preceded by ‘short’ (< or = 5 or < or = 10 ms) and ‘long’ (> 5 or > 10 ms) intervals. 4. When computed from spikes preceded by ‘long’ intervals, PSF amplitudes were small (mean +/‐ S.D., 5.3 +/‐ 2.7%) and onset latencies measured by cusum ranged between 2.4 and 5.4 ms. This is longer than the estimated minimal latency of monosynaptic facilitatory effect on neck EMG (1.9‐2.1 ms). 5. Relative amplitudes of PSF obtained with spikes preceded by ‘short’ intervals were much larger (mean +/‐ S.D., 14.8 +/‐ 7.4%), but cusums indicated negative latencies for four of six PSFs. The unrealistically short onset latencies could be accounted for by the summation of facilitation from the trigger spike with that of the preceding spikes. In four of five TRSNs a large increase of PSF amplitude (from 3.2 to 7.2 times the amplitude obtained from ‘long’ intervals) suggests the presence of frequency‐dependent potentiation of synaptic transmission. 6. This study unequivocally demonstrates that some TRSNs produce significant post‐spike facilitation of neck motoneurones. This facilitation could be mediated by monosynaptic tectomotoneuronal connections although a contribution by disynaptic connections cannot be definitively ruled out. The high instantaneous firing rates of TRSNs produce a potentiation of the otherwise weak facilitatory action of TRSNs that presumably contributes to a rapid recruitment of motoneurones during initiation of head orienting movements.