Neurotransmitter profile of saccadic omnipause neurons in nucleus raphe interpositus

Abstract

Saccadic omnipause neurons (OPNs) are essential for the generation of saccadic eye movements. In primates OPNs are located near the midline within the nucleus raphe interpositus (rip). In the present study we used several different neuroanatomical methods to investigate the transmitters associated with OPNs in the monkey. Immunolabeling for the calcium-binding protein parvalbumin was employed to mark OPNs in the monkey and define the homologous cell group in cat and human. The use of antibodies against GABA, glycine (GLY), glutamate (GLU), serotonin (5-HT), and tyrosine hydroxylase revealed that the somata of OPNs are GLY immunoreactive, but they are devoid of GABA and 5-HT immunostaining. In situ hybridization with the GAD67 mRNA probe confirmed the negative GABA immunostaining of OPNs. 3H-GLY was injected into a projection field of OPNs, the rostral interstitial nucleus of the medial longitudinal fascicle (riMLF)--the vertical saccadic burst neuron area. This resulted in selective retrograde labeling of the OPNs in rip, while no labeling was found in the superior colliculus, which sends an excitatory projection to the riMLF. The somata and dendrites of putative burst neurons in the riMLF were contacted by numerous GLY- immunoreactive terminals. The quantitative analysis of immunoreactive terminal-like structures contacting OPNs revealed a strong input from GLY- and GABA-positive terminals on somata and dendrites, whereas GLU- positive puncta were mainly confined to the dendrites. Very few 5-HT and catecholaminergic terminals contacted OPN somata. Our findings suggest that OPNs use GLY as a neurotransmitter, and they receive numerous contacts from GABAergic, glycinergic, and glutaminergic afferents, and significantly fewer from monoaminergic inputs.

Threshold mechanism for saccade initiation in frontal eye field and superior colliculus

“…While SEF neurons alone do not demonstrate activity consistent with a saccade threshold (So and Stuphorn 2010;Stuphorn et al 2010), if considered as part of a larger oculomotor network, higher FEF and SC presaccadic motor discharge in the prosaccade task could be balanced by higher SEF presaccadic motor discharge in the antisaccade task, at the level of the brain stem saccade-generating circuit downstream of the SC. In the brain stem saccade-generating circuit, omnipause neurons (OPN) are located near the midline of the caudal pontine reticular formation within the nucleus raphe interpositus (Büttner-Ennever et al 1988;Langer and Kaneko 1990) and are associated with tonic activity that inhibits saccade generation (Horn et al 1994;Keller 1974;Scudder et al 2002). OPN must therefore be inhibited to generate a saccade in any direction (Everling et al 1998b;Keller et al 1996).…”

Evidence That the Superior Colliculus Participates in the Feedback Control of Saccadic Eye Movements

“…Certainly, when agents that reduce alertness, such as diazepam (a member of the benzodiazepine group), are administered systemically to primates, saccades are slowed (Jürgens et al 1981). Indeed, benzodiazepine, like muscimol, binds at the GABA A receptor complex (Squires 1988), which has been demonstrated to occur on OPNs (Horn et al 1994). Like diazepam, systemic administration of the sedating drug diphenhydramin also decreases saccadic velocity but does not affect saccadic accuracy (Hopfenbeck et al 1995).…”

Macaque Pontine Omnipause Neurons Play No Direct Role in the Generation of Eye Blinks

“…It is possible that their electrical stimulation was activating other nearby raphe nuclei or their afferents/efferents. The nucleus raphe magnus lies just ventral of the nucleus raphe interpositus (Horn et al 1994) and has a known role in rat blink excitability (Basso and Evinger 1996). A suppressive effect caused by the antidromic stimulation of cells projecting to the OPNs is also possible.…”