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THE ROLE of CEREBRO-PONTO-Cerebellar PATHWAYS in the CONTROL of VERGENCE EYE MOVEMENTS

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THE ROLE of CEREBRO-PONTO-Cerebellar PATHWAYS in the CONTROL of VERGENCE EYE MOVEMENTS THE ROLE OF CEREBRO-PONTO-CEREBElLAR PATHWAYS IN THE CONTROL OF VERGENCE EYE MOVEMENTS PAUL D. R. GAMLIN, KYUNGHEE YOON and HONGYU ZHANG Birmingham, Alabama SUMMARY major sensory drives for vergence and accommoda­ 1 Single-unit recording and anatomical techniques have tion are disparity and blur, -5 looming cues may also 6 7 been used in Rhesus monkeys to investigate the central affect these eye movements. , It has been known for pathways involved in the neural control of vergence many years that the vergence and accommodation and ocular accommodation. Anatomical studies have systems are cross-coupled (see, for example, Fin­ 1 revealed connections between the midbrain near­ cham and Walton and Miiller8), but this cross­ response region and the posterior interposed (IP) and coupling was firstclearly described in its current form fastigial nuclei of the cerebellum. Single-unit recording by Westheimer.9 A simplified version of a recent studies in the IP of alert, trained monkeys identified cross-coupled model of vergence and accommoda­ 1O cells with activity that increased with increases in the tion is shown in Fig. l. When disparity is open-loop, amplitude of divergence and far accommodation, i.e. blur-driven accommodation elicits convergence. the far-response. Microstimulation at the site of these When blur is open-loop, disparity-driven conver­ neurons often produced a far-response. Single-unit gence elicits accommodation. Also, to account for the recording from a precerebellar nucleus, the nucleus observation that vergence and accommodation show reticularis tegmenti pontis (NRTP), identified some tonic adaptation (see, for example, SchorlO and cells with activity that linearly increased with increases Morley et aIY), the model incorporates slow neural in the amplitude of the near-response, and some with integrators as well as fast neural integrators. activity that linearly increased with increases in the amplitude of the far-response. Microstimulation at the site of these near- or far-response neurons often TARGET DISTANCE ACCOMMODATION produced changes in vergence angle and accommoda­ -- tion. Single-unit recording studies in the region of the frontal eye fields identified cells in the pre arcuate cortex with activity that is modulated by either the near- or far-response. These results suggest that regions of the prearcuate cortex, the NRTP and the IP form TA VERGENCE part of a cerebro-ponto-cerebellar pathway modulating BINOCUlAR­� or controlling vergence and ocular accommodation. SUBTENSE Whenever eye movements are made between objects located at different distances, changes in vergence Fig. 1. A current model of the proposed cross-coupling angle and accommodation are required. For exam­ between the vergence and accommodation systems. When disparity is open-loop (equivalent to opening the lower ple, when looking from a far to a near object, switch), blur-driven accommodation elicits convergence; appropriate increases in convergence and accommo­ this is known as accommodative convergence and is dation ensure that the object is imaged on the fovea represented by AC. When blur is open-loop (equivalent to of each eye and is correctly focused. While the two opening the upper switch), disparity-driven convergence elicits accommodation; this is known as convergence Correspondence to: Dr Paul Gamlin, Vision Science Research accommodation and is represented by CA. FAI, fast Center, 626 Worrell Building, University of Alabama at accommodation integrator; FVI, fast vergence integrator; Birmingham, Birmingham, AL 35294, USA. Fax: +1 (205) 934 SAl, slow accommodation integrator; SVI, slow vergence 5725. integrator. (1996) 10, 167-171 Eye © 1996 Royal College of Ophthalmologists 168 P. D. R. GAMLIN ET AL. A c OMA ______�A ______-- _________ VL ____________ __-- _______ VL __ HR HL � ============�======�f VA VA ========= �;= ;=' F === � �:100 Q 50 o TIME (oecondo) B +2MA o ·2MA _________________________ VL VL _________________________ HL====================== HR HRHL �=======�======�======= �' ' F �:��========;=============� F ��========��=========== � 100 � �:100 Q 50 Q 50 o o o 1 I TIME 2 (_do) TIME(oecondo) Fig. 2. The behaviour of a far-response cell in the posterior interposed nucleus (IP). Panel A shows that the activity of this cell is modulated during sine wave tracking of a target moving in depth. Panels B-D show the behaviour of this cell in response to a target with different disparity and blur demands. During these trials, the animal is required to look to the target only after the fixation light is extinguished. Thus there is a period time, which is under experimental control, where the target is illuminated and the animal is required not to look away from the initial fixation target. The randomly timed target appearance, indicated by the step in the lowest trace, has been aligned to I second in all trials to facilitate comparison. In this example, +2 MA is approximately equivalent to a +40 and +2 dioptre demand, while -2 MA is approximately equivalent to a -4° and -2 dioptre demand. DV, divergence velocity; HL, horizontal left eye position; HR, horizontal right eye position; V A, vergence angle; VL, vertical left eye position. Over the past few years, we have acquired own independent accommodative and vergence extensive knowledge of the behavioural character­ demand. istics of vergence and accommodation and their ROLE OF THE CEREBELLUM IN VERGENCE interactions,1-5,10,1l but have only limited knowledge of the neural bases of these eye movements. Most AND ACCOMMODATION studies of the neural control of vergence and ocular The supraoculomotor area and adjacent reticular accommodation have concentrated on the behaviour formation around the oculomotor nucleus contain of either the motoneurons for vergence eye move­ premotor neurons for vergence and ocular accom­ ments,12-16 or the premotor neurons found around modationp-21 We have carried out anatomical the oculomotor nucleus in the supraoculomotor area studies to investigate the inputs to this region, and and adjacent reticular formation.ll,17-21 This report have found connections between it and specific deep reviews our recent efforts to describe more fully the cerebellar nuclei.25 Injections of wheat germ agglu­ central neural pathways involved in the control of tinin/horseradish peroxidase (WGA-HRP) were vergence and accommodation. placed under physiological guidance into this mid­ The studies described below used alert, trained, brain region. These injections resulted in retro­ juvenile Rhesus macaque monkeys (Macaca gradely labelled cells in the deep cerebellular nuclei mulatta). All procedures were approved by the that were predominantly confined to the posterior IACUC, complied with the USPHS Policy on interposed nucleus (IP) and the fastigial nucleus. We Humane Care and Use of Laboratory Animals, and subsequently injected WGA-HRP into these deep have been described previously.22,23 The optical cerebellar nuclei to �se the anterograde capabilities system used in these studies was a binocular visual of this tracer to define their midbrain projections. stimulator similar to one used previously by us22 and Injections of IP resulted in labelled terminals in the based on the original design of Crane and Clark?4 supraoculomotor area but not in the Edinger­ However, it was modified to allow video displays to Westphal nucleus. Fastigial nucleus injections be used for target presentation, with each having its resulted in labelled terminals in a band along the· NEURAL CONTROL OF VERGENCE EYE MOVEMENTS 169 .----. _ ,----, .iMA border between the oculomotor nucleus and the A B VL------' VL- - - 1- supraoculomotor area that included the Edinger­ HR� Westphal nucleus. These anatomical experiments HL� � thus revealed a clear pattern of connections that VA could underlie the cerebellar modulation of vergence 200 20 � � ��1\, and accommodation. �lo� h � � 1 We therefore undertook single-unit recording ] 1 2 345 101 23456 O�����,����,����_ TIME studies of one of the identified deep cerebellar o (seconds) TIME (seconds) nuclei, the posterior interposed nucleus. These studies revealed tonically active cells in a localised Fig. 3. Panel A shows the behaviour of a near-response cell in the nucleus reticularis tegmenti pontis (NRTP) during region of the IP whose activity was modulated as a sine wave tracking in depth. Panel B shows the behaviour of function of the velocity of divergence and far a far-re�ponse cell in NRPT during sine wave tracking in accommodation, i.e. the dynamics of the far­ depth. response?6.27 In addition, most cells encountered displayed a tonic firing rate that decreased as a ROLE OF THE NRTP IN VERGENCE AND function of near viewing. The activity of some of ACCOMMODATION these IP neurons was tested during normal viewing, Given the activity related to the far-response that disparity vergence (blur open-loop) and accommo­ was recorded from neurons of the IP, we decided to dative vergence (disparity open-loop). In all cases, identify those pre cerebellar nuclei that might be firing rate was modulated under all viewing condi­ providing the input to this nucleus. Single-unit tions. Therefore, these cells would be expected to be recording from one precerebellar nucleus, the located after the cross-links that couple blur and nucleus reticularis tegmenti pontis (NRTP), identi­ disparity to vergence and accommodation. Micro­ fied some cells that were related to convergence and stimulation in this region of IP produced divergence some to divergence.23 The convergence-related
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