Brainstem Circuits Triggering Saccades and Fixation.

Omnipause neurons (OPNs) in the nucleus raphe interpositus have tonic activity while the eyes are stationary ("fixation") but stop firing immediately before and during saccades. To locate the source of suppression, we analyzed synaptic inputs from the rostral and caudal superior colliculi (SCs) to OPNs by using intracellular recording and staining, and investigated pathways transmitting the inputs in anesthetized cats of both sexes. Electrophysiologically or morphologically identified OPNs received monosynaptic excitation from the rostral SCs with contralateral dominance, and received disynaptic inhibition from the caudal SCs with ipsilateral dominance. Cutting the tectoreticular tract transversely between the contralateral OPN and inhibitory burst neuron (IBN) regions eliminated inhibition from the caudal SCs, but not excitation from the rostral SCs in OPNs. In contrast, a midline section between IBN regions eliminated disynaptic inhibition in OPNs from the caudal SCs but did not affect the monosynaptic excitation from the rostral SCs. Stimulation of the contralateral IBN region evoked monosynaptic inhibition in OPNs, which was facilitated by preconditioning SC stimulation. Three-dimensional reconstruction of HRP-stained cells revealed that individual OPNs have axons that terminate in the opposite IBN area, while individual IBNs have axon collaterals to the opposite OPN area. These results show that there are differences in the neural circuit from the rostral and caudal SCs to the brainstem premotor circuitry and that IBNs suppress OPNs immediately before and during saccades. Thus, the IBNs, which are activated by caudal SC saccade neurons, shut down OPN firing and help to trigger saccades and suppress ("latch") OPN activity during saccades.SIGNIFICANCE STATEMENT Saccades are the fastest eye movements to redirect gaze to an object of interest and bring its image on the fovea for fixation. Burst neurons (BNs) and omnipause neurons (OPNs) which behave reciprocally in the brainstem, are important for saccade generation and fixation. This study investigated unsolved important questions about where these neurons receive command signals and how they interact for initiating saccades from visual fixation. The results show that the rostral superior colliculi (SCs) excite OPNs monosynaptically for fixation, whereas the caudal SCs monosynaptically excite inhibitory BNs, which then directly inhibit OPNs for the initiation of saccades. This inhibition from the caudal SCs may account for the omnipause behavior of OPNs for initiation and maintenance of saccades in all directions.

Brainstem neural circuits for fixation and generation of saccadic eye movements.

We review neural connections of the superior colliculus (SC) and brainstem saccade-related neurons in relation to saccade generation mechanism. The caudal and rostral SC play a role in saccade generation and visual fixation, respectively. This functional differentiation suggests that different connections should exist between these two SC areas and their brainstem target neurons. We examined synaptic potentials evoked by stimulation of the rostral and caudal SC in inhibitory burst neurons (IBNs) and omnipause neurons (OPNs) in anesthetized cats. The caudal and rostral SC produced monosynaptic excitation and disynaptic inhibition in IBNs, respectively. Intracellular HRP staining showed that single IBNs sent their axons to abducens motoneurons, IBNs and OPNs on the opposite side. OPNs received monosynaptic excitation from the rostral SC, and disynaptic inhibition from the caudal SC via opposite IBNs. These neural connections are discussed in relation to the saccade triggering system and the model proposed by Miura and Optican.

Convergent synaptic inputs from the caudal fastigial nucleus and the superior colliculus onto pontine and pontomedullary reticulospinal neurons.

The caudal fastigial nucleus (FN) is known to be related to the control of eye movements and projects mainly to the contralateral reticular nuclei where excitatory and inhibitory burst neurons for saccades exist [the caudal portion of the nucleus reticularis pontis caudalis (NRPc), and the rostral portion of the nucleus reticularis gigantocellularis (NRG) respectively]. However, the exact reticular neurons targeted by caudal fastigioreticular cells remain unknown. We tried to determine the target reticular neurons of the caudal FN and superior colliculus (SC) by recording intracellular potentials from neurons in the NRPc and NRG of anesthetized cats. Neurons in the rostral NRG received bilateral, monosynaptic excitation from the caudal FNs, with contralateral predominance. They also received strong monosynaptic excitation from the rostral and caudal contralateral SC, and disynaptic excitation from the rostral ipsilateral SC. These reticular neurons with caudal fastigial monosynaptic excitation were not activated antidromically from the contralateral abducens nucleus, but most of them were reticulospinal neurons (RSNs) that were activated antidromically from the cervical cord. RSNs in the caudal NRPc received very weak monosynaptic excitation from only the contralateral caudal FN, and received either monosynaptic excitation only from the contralateral caudal SC, or monosynaptic and disynaptic excitation from the contralateral caudal and ipsilateral rostral SC, respectively. These results suggest that the caudal FN helps to control also head movements via RSNs targeted by the SC, and these RSNs with SC topographic input play different functional roles in head movements.

Neural substrate for suppression of omnipause neurons at the onset of saccades.

The saccade trigger signal was proposed by D.A. Robinson, but neural substrates for triggering saccades by inhibiting omnipause neuron (OPN) activity still remain controversial. We investigated tectal inputs to OPNs by recording intracellular potentials from OPNs and inhibitory burst neurons (IBNs) and searched for interneurons to inhibit OPNs in the brainstem of anesthetized cats. IBNs received monosynaptic excitation from the contralateral caudal superior colliculus (SC) and disynaptic inhibition via contralateral IBNs from the ipsilateral caudal SC, whereas IBNs received disynaptic inhibition from the rostral SC. The latter disynaptic inhibition was mediated by OPNs, since OPNs received monosynaptic excitation from the rostral SC and projected to IBNs. In contrast, OPNs received disynaptic inhibition from the caudal SC. This disynaptic inhibition from the caudal SC was mediated to OPNs by IBNs. These findings suggested possible roles of IBNs for triggering and maintaining saccades by actively inhibiting the tonic activity of OPNs.

Neural circuits for triggering saccades in the brainstem.

Here we review the functional anatomy of brainstem circuits important for triggering saccades. Whereas the rostral part of the superior colliculus (SC) is considered to be involved in visual fixation, the caudal part of the SC plays an important role in generation of saccades. We determined the neural connections from the rostral and caudal parts of the SC to inhibitory burst neurons (IBNs) and omnipause neurons (OPNs) in the nucleus raphe interpositus. To reveal the neural mechanisms of triggering saccadic eye movements, we analysed the effects of stimulation of the SC on intracellular potentials recorded from IBNs and OPNs in anaesthetized cats. Our studies show that IBNs receive monosynaptic excitation from the contralateral caudal SC, and disynaptic inhibition from the ipsilateral caudal SC, via contralateral IBNs. Further, IBNs receive disynaptic inhibition from the rostral part of the SC, on either side, via OPNs. Intracellular recording revealed that OPNs receive excitation from the rostral parts of the bilateral SCs, and disynaptic inhibition from the caudal SC mainly via IBNs. The neural connections determined in this study are consistent with the notion that the "fixation zone" is localized in the rostral SC, and suggest that IBNs, which receive monosynaptic excitation from the caudal "saccade zone," may inhibit tonic activity of OPNs and thereby trigger saccades.

Neural organization of the pathways from the superior colliculus to trochlear motoneurons.

The neural organization of the pathways from the superior colliculus (SC) to trochlear motoneurons was analyzed in anesthetized cats using intracellular recording and transneuronal labeling techniques. Stimulation of the ipsilateral or contralateral SC evoked excitation and inhibition in trochlear motoneurons with latencies of 1.1-2.3 and 1.1-3.8 ms, respectively, suggesting that the earliest components of excitation and inhibition were disynaptic. A midline section between the two SCs revealed that ipsi- and contralateral SC stimulation evoked disynaptic excitation and inhibition in trochlear motoneurons, respectively. Premotor neurons labeled transneuronally after application of wheat germ agglutinin-conjugated horseradish peroxidase into the trochlear nerve were mainly distributed ipsilaterally in the Forel's field H (FFH) and bilaterally in the interstitial nucleus of Cajal (INC). Consequently, we investigated these two likely intermediaries between the SC and trochlear nucleus electrophysiologically. Stimulation of the FFH evoked ipsilateral mono- and disynaptic excitation and contralateral disynaptic inhibition in trochlear motoneurons. Preconditioning stimulation of the ipsilateral SC facilitated FFH-evoked monosynaptic excitation. Stimulation of the INC evoked ipsilateral monosynaptic excitation and inhibition, and contralateral monosynaptic inhibition in trochlear motoneurons. Preconditioning stimulation of the contralateral SC facilitated contralateral INC-evoked monosynaptic inhibition. These results revealed a reciprocal input pattern from the SCs to vertical ocular motoneurons in the saccadic system; trochlear motoneurons received disynaptic excitation from the ipsilateral SC via ipsilateral FFH neurons and disynaptic inhibition from the contralateral SC via contralateral INC neurons. These inhibitory INC neurons were considered to be a counterpart of inhibitory burst neurons in the horizontal saccadic system.

Long descending motor tract axons and their control of neck and axial muscles.

It has been tacitly assumed that a long descending motor tract axon consists of a private line connecting the cell of origin to a single muscle, as a motoneuron innervates a single muscle. However, this notion of a long descending motor tract referred to as a private line is no longer tenable, since recent studies have showed that axons of all major long descending motor tracts send their axon collaterals to multiple spinal segments, suggesting that they may exert simultaneous influences on different groups of spinal interneurons and motoneurons of multiple muscles. The long descending motor systems are divided into two groups, the medial and the lateral systems including interneurons and motoneurons. In this chapter, we focus mainly on the medial system (vestibulospinal, reticulospinal and tectospinal systems) in relation to movement control of the neck, describe the intraspinal morphologies of single long descending motor tract axons that are stained with intracellular injection of horseradish peroxidase, and provide evidence that single long motor-tract neurons are implicated in the neural implementation of functional synergies for head movements.

Vestibular cortical area in the periarcuate cortex: its afferent and efferent projections.

Vestibular input to the periarcuate cortex in the Japanese monkey was examined by analyzing laminar field potentials evoked by electrical stimulation of the vestibular nerve. Vestibular-evoked potentials consisted of early-positive and late-negative potentials and early-negative and late-positive potentials in the superficial and deep layers of the cortex, respectively. They were distributed bilaterally in the periarcuate cortex around the junction of the spur and the arcuate sulcus. This vestibular-projecting area corresponded to the periarcuate area where retrogradely-labeled corticovestibular neurons were distributed after the injection of a tracer into the vestibular nuclei. Comparison of the vestibular-projection area with the distribution of smooth pursuit-related neurons in the same monkey revealed that such neurons existed in the vestibular-projecting area of the periarcuate cortex.

Synaptic inputs and their pathways from fixation and saccade zones of the superior colliculus to inhibitory burst neurons and pause neurons.

The caudal part of the superior colliculus (SC) plays an important role in the generation of saccades, whereas the rostral part of the SC is considered to be involved in visual fixation. The present study was performed to determine neural connections from the rostral and caudal parts of the SC to inhibitory burst neurons (IBNs) and pause neurons (PNs) in the nucleus raphe interpositus in the anesthetized cat, and to reveal the functional role of the rostral SC on eye movements. The intracellular potentials from IBNs and PNs were recorded, and the effects of stimulation of the SC on these neurons were analyzed. The results show that IBNs receive monosynaptic excitation from the contralateral caudal SC, and disynaptic inhibition from the ipsilateral caudal SC via contralateral IBNs. In addition, IBNs receive disynaptic inhibition from the rostral part of the SC on either side via inhibitory interneurons other than IBNs. Intracellular recording from PNs revealed that they receive convergent excitation from the rostral parts of the bilateral superior colliculi and that the rostral SC inhibits IBNs on both sides via PNs. The neural connections determined in this study support the functional independence of the rostral SC and are consistent with the notion that the "fixation zone" is localized in the rostral SC. These results show that the fixation zone in the rostral SC may suppress the initiation of bilateral saccades via pause neurons.

Functional synergies among neck muscles revealed by branching patterns of single long descending motor-tract axons.

In this chapter, we describe our recent work on the divergent properties of single, long descending motor-tract neurons in the spinal cord, using the method of intra-axonal staining with horseradish peroxidase, and serial-section, three-dimensional reconstruction of their axonal trajectories. This work provides evidence that single motor-tract neurons are implicated in the neural implementation of functional synergies for head movements. Our results further show that single medial vestibulospinal tract (MVST) neurons innervate a functional set of multiple neck muscles, and thereby implement a canal-dependent, head-movement synergy. Additionally, both single MVST and reticulospinal axons may have similar innervation patterns for neck muscles, and thereby control the same functional sets of neck muscles. In order to stabilize redundant control systems in which many muscles generate force across several joints, the CNS routinely uses a combination of a control hierarchy and sensory feedback. In addition, in the head-movement system, the elaboration of functional synergies among neck muscles is another strategy, because it helps to decrease the degrees of freedom in this particularly complicated control system.