Abnormal tuning of saccade-related cells in pontine reticular formation of strabismic monkeys

Abstract

Strabismus is a common disorder, characterized by a chronic misalignment of the eyes and numerous visual and oculomotor abnormalities. For example, saccades are often highly disconjugate. For humans with pattern strabismus, the horizontal and vertical disconjugacies vary with eye position. In monkeys, manipulations that disturb binocular vision during the first several weeks of life result in a chronic strabismus with characteristics that closely match those in human patients. Early onset strabismus is associated with altered binocular sensitivity of neurons in visual cortex. Here we test the hypothesis that brain stem circuits specific to saccadic eye movements are abnormal. We targeted the pontine paramedian reticular formation, a structure that directly projects to the ipsilateral abducens nucleus. In normal animals, neurons in this structure are characterized by a high-frequency burst of spikes associated with ipsiversive saccades. We recorded single-unit activity from 84 neurons from four monkeys (two normal, one exotrope, and one esotrope), while they made saccades to a visual target on a tangent screen. All 24 neurons recorded from the normal animals had preferred directions within 30° of pure horizontal. For the strabismic animals, the distribution of preferred directions was normal on one side of the brain, but highly variable on the other. In fact, 12/60 neurons recorded from the strabismic animals preferred vertical saccades. Many also had unusually weak or strong bursts. These data suggest that the loss of corresponding binocular vision during infancy impairs the development of normal tuning characteristics for saccade-related neurons in brain stem.

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.…”

Strabismus and the Oculomotor System: Insights from Macaque Models

“…In normal monkeys, the excitatory burst neurons (EBNs) in the PPRF encode the horizontal component of saccadic eye movements, and the EBNs in the rostral interstitial nucleus of the medial longitudinal fasciculus encode the vertical component of saccadic eye movements (Fuchs et al 1985, King et al 1981, Luschei & Fuchs 1972). Two studies by Walton and colleagues (Walton & Mustari 2015, Walton et al 2013) have examined the PPRF in strabismic monkeys and found deviation from normal characteristics. Electrical stimulation of the PPRF in normal monkeys results in a characteristic horizontal conjugate movement of the two eyes toward the side of the stimulation.…”

“…Further, the horizontal and vertical components of the movement of the two eyes are frequently unequal (i.e., disconjugate eye movements were elicited by electrical stimulation). Neural recordings from EBNs in the PPRF have also shown that many neurons have a preferred direction that is significantly deviated from horizontal (Walton & Mustari 2015). Together, both of these studies suggest that the PPRF is not calibrated in strabismic monkeys to resemble the normal monkey.…”

“…Rather, it may be organized to be even more monocular than observed in normal monkeys (Zhou & King 1998). Further, it has been hypothesized that the observed deviations in the PPRF and cross-coupling between horizontal and vertical saccade generators could be the sources of disconjugate saccadic eye movements and A and V patterns of strabismus (Walton & Mustari 2015). The examination of saccadic cross-coupling in humans with strabismus has provided support for this hypothesis (Ghasia et al 2015).…”

Activity of near-response cells during disconjugate saccades in strabismic monkeys

“…Of particular interest in the present study is the observation that horizontal saccade amplitude typically differs for the two eyes. Studies employing a nonhuman primate model of the disorder have provided compelling evidence that this abnormality is associated with abnormalities in saccade-related areas of brain stem (Fleuriet et al 2016;Upadhyaya et al 2017a;Walton and Mustari 2015;Walton et al 2013).…”