Electrical stimulation of superior colliculus affects strabismus angle in monkey models for strabismus

Abstract

Disruption of binocular vision during the critical period for development leads to eye misalignment in humans and in monkey models. We have previously suggested that disruption within a vergence circuit could be the neural basis for strabismus. Electrical stimulation in the rostral superior colliculus (rSC) leads to vergence eye movements in normal monkeys. Therefore, the purpose of this study was to investigate the effect of SC stimulation on eye misalignment in strabismic monkeys. Electrical stimulation was delivered to 51 sites in the intermediate and deep layers of the SC (400 Hz, 0.5-s duration, 10-40 μA) in 3 adult optical prism-reared strabismic monkeys. Scleral search coils were used to measure movements of both eyes during a fixation task. Staircase saccades with horizontal and vertical components were elicited by stimulation as predicted from the SC topographic map. Electrical stimulation also resulted in significant changes in horizontal strabismus angle, i.e., a shift toward exotropia/esotropia depending on stimulation site. Electrically evoked saccade vector amplitude in the two eyes was not significantly different ( > 0.05; paired -test) but saccade direction differed. However, saccade disconjugacy accounted for only ~50% of the change in horizontal misalignment while disconjugate postsaccadic movements accounted for the other ~50% of the change in misalignment due to electrical stimulation. In summary, our data suggest that electrical stimulation of the SC of strabismic monkeys produces a change in horizontal eye alignment that is due to a combination of disconjugate saccadic eye movements and disconjugate postsaccadic movements. Electrical stimulation of the superior colliculus in strabismic monkeys results in a change in eye misalignment. These data support the notion of developmental disruption of vergence circuits leading to maintenance of eye misalignment in strabismus.

Response Properties of Cells Within the Rostral Superior Colliculus of Strabismic Monkeys

“…3 Recent data from animal models of strabismus acquired using neurophysiological methods such as electrical stimulation, muscimol inactivation, and single cell recording within numerous brain areas including the motor nuclei, supraoculomotor area (SOA), fastigial and posterior interposed nuclei of the cerebellum, paramedian pontine reticular formation (PPRF), and the superior colliculus (SC), have shown that various structures within a vergence neural circuit contributes toward maintenance of the state of strabismus. [4][5][6][7][8][9][10][11] The SC has been extensively studied for its involvement in saccadic eye movements, [12][13][14] and this structure also appears to have a role in vergence. Van Horn et al, 15 in a study in normal monkeys, have shown that the rostral SC (rSC) contains vergence related neurons (convergence and divergence), which modulate with eye movements made to sinusoidal target motion in depth.…”

“…Electrical stimulation not only evoked staircase saccades but also produced a divergent change in strabismus angle as we have shown in our previously published study. 7 The small amplitude of the electrically evoked saccade at the two sites (panels A-ii [mean: 0.38 6 0.18] and B-ii [mean: 3.68 6 0.38]) indicate that these cells were located in the rostral part of the SC. 12 In these data, the strabismus angle (left eye position -right eye position) is modulated depending on which of the two eyes is fixating (panels A-iii and B-iii), and this property was leveraged to investigate the correlation between strabismus angle and neural response rate within the subpopulation of rSC cells.…”

“…20,21 Motivated by the evidence in normal monkeys and humans, we recently investigated the SC in strabismic monkeys using electrical stimulation techniques and showed that low current electrical stimulation within mostly the rostral part of the SC of strabismic monkeys resulted in a change in strabismus angle. 7 Depending on the site of stimulation, we elicited either convergent or divergent change of strabismus angle. Other studies in strabismic monkeys using SC electrical stimulation have also shown that there were influences on strabismic angle during electrical stimulation.…”

“…10,22,23 Our analysis of the stimulation data indicated that the strabismus angle changes were a consequence of disconjugate saccades and also disconjugate postsaccadic drift. 7 We hypothesized that the disconjugate postsaccadic drift could be the consequence of stimulating a population of vergence (misalignment in the case of strabismic monkeys) cells within the SC. Therefore, the goal of the current study was to identify and examine the response properties of cells within the SC whose firing was potentially related to eye misalignment.…”

Neural plasticity following surgical correction of strabismus in monkeys

“…Neurons within the supra-oculomotor area, which encodes vergence responses in normal animals, were found to encode horizontal misalignment in strabismic monkeys (Das 2012). More recent studies showed that electrical stimulation of the rostral superior colliculus causes a change in strabismus angle (Fleuriet et al 2016) (Upadhyaya et al 2017). Given the weight of evidence supporting a neural substrate for maintenance of strabismus, it is likely that neural plasticity following surgical manipulation of the EOM also contributes to the final strabismic state achieved after surgery.…”