Visual error signals from the pretectal nucleus of the optic tract guide motor learning for smooth pursuit

Abstract

Smooth pursuit (SP) eye movements are used to maintain the image of a moving object on or near the fovea. Visual motion signals aid in driving SP and are necessary for its adaptation. The sources of visual error signals that support SP adaptation are incompletely understood but could involve neurons in cortical and brain stem areas with direction selective visual motion responses. Here we focus on the pretectal nucleus of the optic tract (NOT), which encodes retinal error information during SP. The aim of this study was to characterize the role of the NOT in SP adaptation. SP adaptation is typically produced using a double step of velocity ramp (double-step paradigm), where target speed either increases or decreases 100 ms after the beginning of a trial. In our study, we delivered a brief (200 ms) train of microelectrical stimulation (ES) in the left NOT to introduce directional error signals at the point in time where a second target speed would appear in a double-step paradigm. The target was extinguished coincidentally with the onset of the ES train. Initial eye acceleration (1st 100 ms) showed significant increases after 100 trials, which included left NOT stimulation during ongoing pursuit in an ipsiversive (leftward) direction. In contrast, initial eye acceleration showed significant decreases after repeated left NOT stimulation during contraversive (rightward) SP. Control studies performed using the same periodicity of NOT stimulation as in the preceding text but without accompanying SP did not induce changes in eye acceleration. In contrast, ES of the NOT paired with active SP produced gradual changes in eye acceleration similar to that observed in double-step paradigm. Therefore our findings support the suggestion that the NOT is an important source of visual error information for guiding motor learning during horizontal SP.

Fig. 1.

Histological reconstruction of recording sites. A: line drawing and representative histological section stained for Nissl substance to demonstrate location of electrode tracks. An electrode track reconstructed from histological section is indicated (- - -). → (bottom), an electrode track that was located in the rostrocaudal extent of the pretectum at the level of the pretectal olivary nucleus (PON). NOT, nucleus of the optic tract; PULV, pulvinar. Scale bar = 1 mm. B: response properties of a representative NOT neuron during horizontal large-field visual motion presented on a tangent screen while the monkey (Macaca mulatta) fixated a stationary target spot. A strong direction-selective response occurs at short latency (50 ms) after the start of leftward visual motion. C: directional tuning data for a representative NOT neuron. Large-field visual motion was presented in different directions while the monkeys fixated a stationary target. The average firing rate is indicated at 45° intervals (●), with a curve fit to estimate the direction preference for the unit.

Fig. 2.

Electrical stimulation (ES) of the left NOT using a 10 s train of low current (50 μA) short-duration (200 μs) biphasic pulses at 200 Hz. Nystagmus was elicited at short latency following stimulation at the site indicated in Fig. 1. Immediately following the start of the ES (thick bar, top traces), leftward optokinetic nystagmus (OKN)-like nystagmus begins with slow-phase eye velocity building up during stimulation. First · · · , the onset of the ES.

Fig. 3.

Smooth pursuit adaptation paradigm using microstimulation of NOT. The standard double-step paradigm (top), which was like that used previous studies (e.g., Kahlon and Lisberger 1996; Ono and Mustari 2007; Takagi et al. 2000), has the target moving at one speed for 1st 100 ms followed by either a higher (A) or lower (B) speed. Smooth pursuit adaptation with NOT stimulation (bottom) delivered at the point in time where a second target speed would appear in standard double-step paradigms. The target was extinguished coincidentally with the onset of the ES train to eliminate actual retinal error motion associated with the target. C and D: ipsi- and contraversive target motion, respectively.

Fig. 4.

Representative eye and target motion traces in ipsiversive (top) and contraversive (bottom) directions of smooth pursuit. A and E: control testing using target motion alone. Target motion began moving at 10°/s for 100 ms, and then target was extinguished. B and F: control testing using left NOT stimulation without target motion. The stationary target was extinguished coincidentally with the onset of the NOT stimulation train (200 ms duration; 50 μA). C and G: coupled NOT stimulation with target motion. D and H: comparison of mean eye velocity during three different testing conditions.

Fig. 5.

Adaptation paradigm (top) during left NOT stimulation (200 ms duration; 50 μA) and leftward (ipsiversive) smooth pursuit of a moving target. Average eye acceleration of the 1st 100 ms of tracking in the adaptation paradigm of ipsiversive pursuit were shown as a function of trial number for a representative experiment. Control trials using leftward target motion alone are shown before and after adaptation paradigm. The eye traces in pre- and early adaptation are the same as those illustrated during target motion and ES plus target shown in Fig. 4.

Fig. 6.

Adaptation paradigm (top) during left NOT stimulation (200 ms duration; 50 μA) and rightward (contraversive) smooth pursuit of a moving target. Average eye acceleration during the 1st 100 ms of tracking in the adaptation paradigm associated with contraversive pursuit shown as a function of trial number for a representative experiment. Control trials using rightward target motion alone are shown before and after adaptation paradigm. The eye traces in pre- and early adaptation are same as the trace during target motion and ES plus target shown in Fig. 4.

Fig. 7.

Control paradigm using NOT stimulation without target motion. Average eye acceleration of the 1st 100 ms of tracking in the control paradigm using left NOT stimulation alone (200 ms duration) are shown as a function of trial number for a representative experiment. Eye velocity and acceleration did not change in an adaptive manner across repeated trials of NOT stimulation.

Fig. 8.

Mean eye acceleration during the 1st 100 ms of tracking for 10 trials are shown at 30-trial intervals for 2 monkeys. Ipsi- (A) and contraversive adaptation paradigms (B) and control testing (C) are shown. Eye acceleration during double-step paradigm of step-up (D) and step-down (E) are shown at 50-trial intervals in same subjects. Filled and open circles in A, B, D, and E indicate different monkeys. Half filled symbols and gray symbols in C indicate control testing using target motion alone and NOT stimulation alone, respectively. Different half filled symbols (circle and square) and gray symbols (circle and triangle) indicate different monkeys.

Fig. 9.

Simplified diagram to indicate some of the pathways for NOT and pontine nuclei (PN) derived visual and eye motion signals to the contralateral cerebellum. Horizontal directional retinal error information for smooth pursuit adaptation is available in the NOT. NOT neurons respond preferentially to ipsiversive visual motion and drive neurons in the ipsilateral dorsal cap of Kooy (dck) and the medial accessory olive (MAO) of the inferior olive. For leftward pursuit and left NOT stimulation (ipsiversive pursuit paradigm), the right floccular complex and vermis receive leftward complex spikes and multidirectional simple spikes derived from the PN (e.g., NRTP and DLPN). The arrows indicate that the PN provides multi-directional eye and visual motion signals, while the NOT provides only horizontal visual error signals. Abbreviations; cf., climbing fiber; Floc, flocculus; Mf, mossy fiber; PC, Purkinje cell; Pf, parallel fiber; vPF, ventral paraflocculus.