PURPOSE. To investigate whether neuronal activity within the supraoculomotor area (SOA-monosynaptically connected to medial rectus motoneurons and encode vergence angle) of strabismic monkeys was correlated with the angle of horizontal misalignment and therefore helps to define the state of strabismus. METHODS. Single-cell neural activity was recorded from SOA neurons in two monkeys with exotropia as they performed eye movement tasks during monocular viewing. RESULTS. Horizontal strabismus angle varied depending on eye of fixation (dissociated horizontal deviation) and the activity of SOA cells (n ¼ 35) varied in correlation with the angle of strabismus. Both near-response (cells that showed larger firing rates for smaller angles of exotropia) and far-response (cells that showed lower firing rates for smaller angles of exotropia) cells were identified. SOA cells showed no modulation of activity with changes in conjugate eye position as tested during smooth-pursuit, thereby verifying that the responses were related to binocular misalignment. SOA cell activity was also not correlated with change in horizontal misalignment due to A-patterns of strabismus. Comparison of SOA population activity in strabismic animals and normal monkeys (described in the literature) show that both neural thresholds and neural sensitivities are altered in the strabismic animals compared with the normal animals. CONCLUSIONS. SOA cell activity is important in determining the state of horizontal strabismus, possibly by altering vergence tone in extraocular muscle. The lack of correlated SOA activity with changes in misalignment due to A/V patterns suggest that circuits mediating horizontal strabismus angle and those that mediate A/V patterns are different. (Invest Ophthalmol Vis Sci. 2012;53:3858-3864) DOI:10.1167/iovs.11-9145 I nfantile forms of strabismus occur in as much as 5% of all children. 1-3 The exact cause of strabismus is often unknown. 3-5 Many diverse factors, including refractive errors (anisometropia); visual acuity factors (congenital cataracts); genetic factors (congenital fibrosis of extraocular muscle, Marfan's syndrome); brainstem pathology (Duane's syndrome); and muscle pathology (dysthyroid opthalmopathy), likely trigger a cascade of events that result in misaligned eyes. 2,16,17 In cases of strabismus that is not due to an obvious paralytic or restrictive factor, a common feature among the different trigger factors and correspondingly the different approaches to producing animal models for strabismus is that binocular vision is disrupted in early life due to breakdown in either motor fusion (e.g., surgical strabismus models) or sensory fusion (e.g., optically induced strabismus). Although motoneurons showed correlated activity with abnormal alignment and abnormal eye movements associated with strabismus, it is unlikely that they are the source of the problem. Central structures are likely providing aberrant inputs to motoneurons. When considering sources of such aberrant input to the motoneurons, the supraoculomotor area (SOA) is implicated because of its purported role in binocular eye movements. The SOA is the area immediately adjacent to the oculomotor nucleus. Neurons in this area receive major projections from the fastigial nucleus and the posterior interposed nucleus in the cerebellum, and also project monosynaptically to the medial rectus motoneurons in the oculomotor nucleus
