In the 16 years since we last summarized the behavior of the premotor elements that control saccades, research has revealed shortcomings in previous formulations of the control mechanisms of the brainstem saccadic burst generator. Specifically, complexities in the eye movement plant, a more detailed knowledge of the behaviors of certain bursting neurons, and previously undiscovered anatomical connections have broadened our knowledge but have generated new questions that require rethinking previous concepts. Perhaps the most crucial revelations/insights have come from studies that have implicated the superior colliculus and the midline cerebellum as crucial elements of the burst generator. In summarizing these recent findings here, we have been led to conclude that the superior colliculus issues the saccadic command and receives feedback from the brainstem burst generators, but the feedback does not control saccade size. In addition, the midline cerebellum also contains a feedback path, but only as part of a more generalized circuit that serves multiple functions.

1. Single neurons in the abducens nucleus were recorded extracellularly in alert rhesus macaques trained to make a variety of eye movements. An abducens neurons was identified as a motoneuron (MN) if its action potentials triggered an averaged EMG potential in the lateral rectus muscle. Abducens internuclear neurons (INNs) that project to the oculomotor nucleus were identified by collision block of spontaneous with antidromic action potentials evoked with a stimulating electrode placed in the medial rectus subdivision of the contralateral oculomotor nucleus. 2. All abducens MNs and INNs had qualitatively similar discharge patterns consisting of a burst of spikes for lateral saccades and a steady firing whose rate increased with lateral eye position in excess of a certain threshold. 3. For both MNs and INNs the firing rates associated with different, constant eye positions could be described accurately by a straight line with slope, K (the eye position sensitivity in spikes.s-1.deg-1), and intercept, T (the eye position threshold for steady firing). For different MNs, K increased as T varied from more medial to more lateral values. In contrast, the majority of INNs already were active for values of T more medial than 20 degrees and showed little evidence of recruitment according to K. 4. During horizontal sinusoidal smooth-pursuit eye movements, both MNs and INNs exhibited a sinusoidal modulation in firing rate whose peak preceded eye position. From these firing rate patterns, the component of firing rate related to eye velocity, R (the eye velocity sensitivity in spikes.s-1.deg-1.s-1), was determined. The R for INNs was, on average, 78% larger than that for MNs. Furthermore, R increased with T for MNs, whereas INNs showed no evidence of recruitment according to R. If, as in the cat, the INNs of monkeys provide the major input to medial rectus MNs and if simian medial rectus MNs behave like our abducens MNs, then recruitment order, which is absent in INNs, must be established at the MN pool itself. 5. Unexpectedly, the R of MNs decreased with the frequency of the smooth-pursuit movement. Furthermore, the eye position sensitivity, K, obtained during steady fixations was usually less than that determined during smooth pursuit. Therefore, conclusions about the roles of MNs and premotor neurons based on how their R and K values differ must be viewed with caution if the data have been obtained under different tracking conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

Clinically, it has been reported that chronic pain induces depression, anxiety, and reduced quality of life. The endogenous opioid system has been implicated in nociception, anxiety, and stress. The present study was undertaken to investigate whether chronic pain could induce anxiogenic effects and changes in the opioidergic function in the amygdala in mice. We found that either injection of complete 35 S]GTPgS binding in membranes of the amygdala was significantly suppressed by CFA injection or nerve ligation. CFA injection was associated with a significant increase in the k-opioid receptor agonist 2-(3,4-dichlorophenyl)-N-methyl-35 S]GTPgS binding in membranes of the amygdala. The intracerebroventricular administration and microinjection of a selective m-opioid receptor antagonist, a selective d-opioid receptor antagonist, and the endogenous k-opioid receptor ligand dynorphin A caused a significant anxiogenic effect in mice. We also found that thermal hyperalgesia induced by sciatic nerve ligation was reversed at 8 weeks after surgery. In the light-dark test, the time spent in the lit compartment was not changed at 8 weeks after surgery. Collectively, the present data constitute the first evidence that chronic pain has an anxiogenic effect in mice. This phenomenon may be associated with changes in opioidergic function in the amygdala.

Smooth pursuit and vestibularly induced eye movements interact to maintain the accuracy of eye movements in space (i.e., gaze). To understand the role played by the frontal eye fields in pursuit-vestibular interactions, we examined activity of 110 neurons in the periarcuate areas of head-stabilized Japanese monkeys during pursuit eye movements and passive whole-body rotation. The majority (92%) responded with the peak of their modulation near peak stimulus velocity during suppression of the vestibuloocular reflex (VOR) when the monkeys tracked a target that moved with the same amplitude and phase and in the same plane as the chair. We classified pursuit-related neurons (n = 100) as gaze- velocity if their peak modulation occurred for eye (pursuit) and head (VOR suppression) movements in the same direction; the amplitude of modulation during one less than twice that of the other; and modulation was lower during target-stationary-in-space condition (VOR x1) than during VOR suppression. In addition, we examined responses during VOR enhancement (x2) in which the target moved with equal amplitude as, but opposite direction to, the chair. Gaze-velocity neurons responded maximally for opposite directions during VOR x2 and suppression. Based on these criteria, the majority of pursuit-related neurons (66%) were classified as gaze-velocity with preferred directions uniformly distributed. Because the majority of the remaining cells (32/34) also responded during VOR suppression, they were classified as eye/head-velocity neurons. Thirteen preferred pursuit and VOR suppression in the same direction; 13 in the opposite direction, and 6 showed biphasic modulation during VOR suppression. Eye- and gaze-velocity sensitivity of the two groups of cells were similar; mean (+/- SD) was 0.53 +/- 0.30 and 0.50 +/- 0.44 spikes/s per degrees /s, respectively. Gaze-velocity (but not eye/head-velocity) neurons showed significant correlation between eye- and gaze-velocity sensitivity, and both groups maintained their responses when the tracking target was extinguished briefly. The majority of pursuit-related neurons (28/43 = about 65%) responded to chair rotation in complete darkness. When the monkeys fixated a stationary target, more than half of cells tested (21/40) discharged in proportion to the velocity of retinal motion of a second laser spot (mean velocity sensitivity = 0.20 +/- 0.16 spikes/s per degrees /s). Preferred directions of individual cells to the second spot were similar to those during pursuit. Visual responses to the second spot movement were maintained even when it was extinguished briefly. These results indicate that both retinal image- and gaze-velocity signals are carried by single periarcuate pursuit-related neurons, suggesting that these signals can provide target-velocity-in-space and gaze-velocity commands during pursuit-vestibular interactions.