[Frontiers in Bioscience 2, d552-577, November 15, 1997] 552 THE NEURAL INTEGRATORS OF THE MAMMALIAN SACCADIC SYSTEM A.K. Moschovakis Division of Computational Neuroscience,Institute of Applied and Computational Mathematics, FO.R.T.H., and Dept. Basic Sciences, Faculty of Medicine, University of Crete, P.O. Box 1393, Crete Greece TABLE OF CONTENTS 1. Abstract 2. Introduction 3. Regions 4. Discharge patterns 4.1. NIC neurons 4.2. NPH neurons 4.3. Secondary vestibular neurons 5. Input-output connections 5.1. Comparison MLBs 5.2. MLB projections to the neural integrators 5.3. Comparison with motoneurons 5.4. Integrator projections to motoneurons 5.5. Motoneuronal projections of secondary vestibular neurons 5.6. Connections between the vestibular nuclei, the NIC and the NPH 6. Models 7. Conclusions 8. Acknowledgements 9. References 1. ABSTRACT The neural velocity to position integrators transform the saccade related signal of the burst generators into an eye position related tonic signal they convey to motoneurons. They are largely confined to three heavily interconnected midbrain structures: 1) The interstitial nucleus of Cajal (NIC), 2) The nucleus prepositus hypoglossi (NPH), 3) The vestibular nuclei (VN). Integration in the horizontal and vertical planes is accomplished largely independently by the NPH-VN and the NIC-VN complexes, respectively. Cells in these regions carry a more or less intense phasic signal related to saccades and a tonic signal related to eye position. Depending on the relationship between the rate of their discharge and the position of the eyes, these cells have been further subdivided into regular or irregular, more or less sensitive, and bi-directionally or uni-directionally modulated. The present review provides a brief description of their discharge pattern and that of burst neurons and extraocular motoneurons. Then, evidence concerning the input-output connections of relevant cell classes is summarized. Finally, several modelling attempts to simulate the neural velocity-to-position integrators are presented and their verisimilitude is evaluated in the light of psychophysical, anatomical, physiological and neurological evidence. 2. INTRODUCTION The behavioral repertoire of humans and other animals contains a large variety of ocular movements (convergent, divergent, saccadic, nystagmic ______________________________________________ Received 8/11/97 Accepted 9/29/97 Send correspondence to:A.K. Moschovakis, Dept. Basic Sciences, Faculty of Medicine, University of Crete, P.O. Box 1393, Crete, Greece, Tel.: ++30-81-394509, Fax.: ++30-81-394530, E-mail: moschov@med.uch.gr slow phases and smooth pursuit). The best understood of the relatively independent neural circuits that control them is the one generating saccades (reviewed in ref. 1). These are ubiquitous movements that primates execute at a rate of about 3 per second to rapidly reorient their line of sight towards salient features of the surrounding world. Figure 1 is a schematic overview of the neural machinery that controls saccades. The top part of this figure is devoted to higher order structures such as the superior colliculus (SC) the cortical eye fields (Cx), the thalamus and the basal ganglia (Str/STh/Th/SNR) and the cerebellum (Cb); these structures evaluate the saliency, importance and context of image features and issue commands for the execution of saccades of appropriate direction and amplitude. The command signals are conveyed to the burst generators which determine the metrical and dynamical properties of saccades. The horizontal and vertical size of saccades is separately determined by the horizontal (HBG) and vertical (VBG) burst generators. The former is located in the caudal paramedian pontine reticular formation (PPRF; 2, 3, 4) while the latter occupies the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF; 5, 6, 7, 8). Each burst generator distributes its output to extraocular motoneurons in such a way as to account for eye conjugacy (9), and to other burst generators in such a way as to ensure the push-pull coupling of burst generators with opposite on-directions and the two-dimensional coordination of burst generators with orthogonal on-directions. The output of the saccadic system is carried by extraocular motoneurons (the HMN and VMN blocks of figure 1). These emit a burst of discharge that is proportional to the size of saccades in their preferred direction (left or right, up or down) and then settle into a tonic discharge that is proportional to eye position along