Anatomical Evidence that the Superior Colliculus Controls Saccades through Central Mesencephalic Reticular Formation Gating of Omnipause Neuron Activity

Abstract

Omnipause neurons (OPNs) within the nucleus raphe interpositus (RIP) help gate the transition between fixation and saccadic eye movements by monosynaptically suppressing activity in premotor burst neurons during fixation, and releasing them during saccades. Premotor neuron activity is initiated by excitatory input from the superior colliculus (SC), but how the tectum's saccade-related activity turns off OPNs is not known. Since the central mesencephalic reticular formation (cMRF) is a major SC target, we explored whether this nucleus has the appropriate connections to support tectal gating of OPN activity. In dual-tracer experiments undertaken in macaque monkeys (Macaca fascicularis), cMRF neurons labeled retrogradely from injections into RIP had numerous anterogradely labeled terminals closely associated with them following SC injections. This suggested the presence of an SC-cMRF-RIP pathway. Furthermore, anterograde tracers injected into the cMRF of other macaques labeled axonal terminals in RIP, confirming this cMRF projection. To determine whether the cMRF projections gate OPN activity, postembedding electron microscopic immunochemistry was performed on anterogradely labeled cMRF terminals with antibody to GABA or glycine. Of the terminals analyzed, 51.4% were GABA positive, 35.5% were GABA negative, and most contacted glycinergic cells. In summary, a trans-cMRF pathway connecting the SC to the RIP is present. This pathway contains inhibitory elements that could help gate omnipause activity and allow other tectal drives to induce the bursts of firing in premotor neurons that are necessary for saccades. The non-GABAergic cMRF terminals may derive from fixation units in the cMRF.

A central mesencephalic reticular formation projection to the supraoculomotor area in macaque monkeys

“…The cMRF reticuloraphe neurons projecting to omnipause neurons in the nucleus raphe interpositus have a similar distribution, but are fewer in number (Fig. 11A) (Wang et al 2013). Reticulospinal neurons projecting to cervical spinal cord and medullary reticuloreticular cMRF neurons projecting to the rostral medullary reticular formation occupy just the medial portion of the cMRF (Fig.…”

“…PhaL injections were made using the same general approach. However, the PhaL was dissolved in pH 8.0, 0.1 M phosphate buffer (PB) and was ejected from a glass micropipette with a 15–20 μm tip by iontophoresis under the control of an iontophoretic current supply module (Model CS 3; Transkinetics; Canton, MA, USA), using 7 μA, 7 second, square wave pulses for 10 min at each injection site (see Wang et al, 2013 for details). In the case of the retrograde experiments, the initial approach was similar, however, the aspiration was extended to reveal the posterior commissure.…”

“…BDA was visualized using diaminobenzidine (DAB) as a chromagen in 100 μm sections, as previously described (Adams 1977; Chen and May 2000; Wang et al 2013). Briefly, sections were rinsed with fresh 0.1 M, pH 7.2 PB then 0.05% Triton X-100 in the same PB.…”

“…Specifically, cMRF projections to the cervical cord and to reticulospinal neurons in the medullary reticular formation were demonstrated. Finally, a projection to the omnipause cells in nucleus raphe interpositus has been delineated (Wang et al 2013). This projection derives primarily from GABAergic cMRF cells that receive collicular input, so it may help release paramedian pontine reticular formation (PPRF) burst neuron activity.…”

Response Inhibition

“…Omnipause neurons (OPNs) in the brain stem gate the onset of saccadic eye movements Wang et al, 2013; see Leigh & Zee, 2006 for a review). OPNs receive projections from the fixation neurons in the superior colliculus (SC), which in turn receive projections from the fixation neurons in the frontal eye field (FEF).…”