whose activity will be reduced by the decision to start a saccade as well as by the growing activity of the EBNs. Conversely, during fixation, the inhibition from OPNs will tend to suppress spurious activation of EBNs and thereby unintended saccades (fig. 4).

The Superior Colliculus

The brainstem burst generators in the PPRF and the MRF receive input from a number of brain structures such as the SC, the FEFs and the oculomotor cerebellum. The input from the SC, homologue of the optic tectum in amphibians and fishes, is probably the most important and, moreover, the best understood source of input. The SC is a multilayered structure whose intermediate layer plays a critical role in the control of visual fixation and saccadic eye movements, serving as the key structure underlying the spatiotemporal transformation for saccades. Neurons in the intermediate layer of the SC show convergence of visual, auditory, and somatosensory informations, integrated to guided saccades but also other types of orientation behavior [55–59]. The role of the intermediate layer of the SC in the guidance of saccades has first been established by electrical microstimulation [60], which evokes saccades into the contralateral hemifield with amplitudes and directions fully determined by the location of the microelectrode in the SC (fig. 5). Large saccades are elicited by microstimulation of the caudal SC, whereas small saccades are evoked by microstimulation of its more rostral part. Moving the stimulation microelectrode gradually within the intermediate layer leads to gradual changes in the metrics of evoked saccades, demonstrating that the intermediate layer of the SC contains a topographic map of saccade endpoints. The location of the endpoint of evoked saccades coincides with the location of the circumscribed movement fields of saccade-related burst neurons, found at the respective location in the intermediate layer. Moreover, the map of saccade endpoints in the intermediate layer is congruent with the retinotopic map in the overlying, purely visual superficial layer of the SC. Three other types of neurons characterize the intermediate layer of the SC. In addition to the burst neurons (SC-BNs), which are purely saccade-related, lacking any visual responses, the intermediate layer also houses purely visual as well as mixed visuomotor neurons. One variety of the latter, the so-called build-up cells play a decisive role in current models of the role of the SC in the generation of saccades. Unlike the visual and the burst cells, they are characterized by open response fields that lead to their activation by any saccade in their preferred direction, independent of amplitude. The rostral pole of the SC, adjoining to the small saccade representation, is special as it contains neurons (SC-FNs) that are active during fixation, rather than being

Fig. 5. The superior collicular map for saccades. a The rostral-caudal (thin lines) axis represents the saccade horizontal component, while the vertical component is represented by the mediolateral axis (thick lines). b Discharge of a SC-BN and discharge of a SC-FN during a 15 saccade.

activated by saccades. Conversely, these fixation neurons are silent during saccades. While the fixation zone maintains an excitatory projection to the brainstem omnipause region, the burst neurons project to the brainstem burst generators via LLBNs in the midbrain. The decision to carry out a saccade of a given amplitude and direction will activate the neurons at the corresponding location in the SC map, while at the same time inhibiting the SC fixation zone (fig. 5b). Excitatory drive will be passed on from this location to the EBNs by way of the LLBNs. At the same time, activity from this initial location in the SC spreads to buildup neurons in neighboring locations representing smaller amplitudes which will sustain the excitation of the brainstem burst generator. The drive of the EBNs will come to an end, once the spread of activity on the collicular map has reached the fixation zone, on the one hand, stopping EBNs directly, and on the other hand, activating OPNs. In sum, the spatiotemporal transformation for saccades is a direct consequence of the functional architecture of the SC and its connections with the brainstem (fig. 5).

The scheme sketched out before is a simplification of more elaborated models on the role of the SC in the generation of saccades [61, 62]. Although based on an abundance of anatomical and physiological observation, they still contain a number of speculative and highly controversial elements. Alternative views on the role of the SC in saccades that have recently been proposed suggest a direct involvement in the feedback control of saccades [63, 64] or the elaboration of the ‘error signal’ needed in order to adjust the oculomotor plant

[65–67]. Bergeron et al. [67] proposed, in extension of the original assumption of Robinson [60], that the SC encodes the distance to the target rather than saccade amplitude. Distance to target is given by comparing target position on the retina with current gaze position, yielding the gaze shift needed (gaze position error) to fovealize the target. The important difference with respect to the original Robinson model is that the variable controlled is gaze, the sum of eye and head position, rather than just eye position and, secondly, that the SC is inside the feedback loop calculating the motor error.

The Basal Ganglia

The interest in the role of the basal ganglia in the control of saccadic eye movements emerged after saccade-related neurons had been demonstrated in various parts of the basal ganglia [68, 69] and, moreover, a direct projection from the substantia nigra pars reticulata (SNr) to the SC had been established [70]. This inhibitory projection is in turn under the control of an inhibitory projection coming from the caudate nucleus (CN). One of the main functions of the basal ganglia in the control of saccades seems to be the avoidance of unwanted saccades. This is demonstrated by the emergence of spurious saccades, if the tonic inhibitory input is blocked experimentally (fig. 6) [71]. For instance, in order to suppress too early saccades in a memory-guided saccade task the SNr continuously inhibits the SC-BN in the intermediate layer of the SC [71, 72]. If the context allows the execution of the saccade, the CN via its negative action on the SNr will disinhibit the SC-BN [73], allowing the SC-BN to fire and start a saccade (fig. 6).

The Oculomotor Role of the Pontine Nuclei and the

Nucleus Reticularis Tegmenti Pontis

Both cortical structures we dispose of, cerebral cortex and cerebellar cortex are involved in the control of saccades. The major pathway linking the two cortices, including those areas involved in saccades, is the cerebropontocerebellar projection with the pontine nuclei (PN) in the basilar brainstem serving as intermediate station. In addition to input from saccade-related areas of the cerebral cortex such as area LIP and the FEF, the PN also receive visual and eye movement-related input from the SC. Accordingly, the PN may be regarded as a central integration unit in a major pathway subserving saccades. In this section, we will describe the role of the PN in saccades and in addition discuss the role of a neighboring major precerebellar nucleus, the nucleus reticularis tegmenti

a b

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Fig. 6. a Scheme of the inhibitory projection from the basal ganglia to the SC. b The injection of the GABA antagonist (bicuculine) into the SC suppresses the inhibition and thereby induces spurious saccades shown in (c). c Saccadic jerks during fixation of a central target after injection of bicuculine into the left SC while the monkey waits for the signal to make a saccade to a memorized spatial location. The vertical line marks the end of the presence of the fixation target. Upper traces show horizontal and lower traces vertical eye position. From Hikosaka and Wurtz [71], with permission.