ORIGINAL RESEARCH article
Front. Neuroanat.
Transmitter-and ion channel profiles of saccadic omnipause neurons and cholinergic non-omnipause neurons in human nucleus raphe interpositus
Provisionally accepted
Ümit Suat Mayadali1
Maximilian John2Michael Abspacher1
Christoph Schmitz3
Aasef G Shaikh4
Anja Kerstin Ellen Horn5*- 1Institute of Anatomy and Cell Biology, Dept. I, Ludwig Maximilian University of Munich, Munich, Germany
- 2Institute of Anatomy I, Faculty of Medicine, Ludwig Maximilian University of Munich, Munich, Germany
- 3Institute of Anatomy II, Faculty of Medicine, Ludwig Maximilian University of Munich, Munich, Germany
- 4Dept. of Neurology, Case Western Reserve University,, Cleveland, United States
- 5Institute of Anatomy I, Ludwig Maximilian University of Munich, Munich, Germany
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Background: Omnipause neurons (OPN) are glycinergic neurons that tonically inhibit burst neurons between saccades. In primates, OPNs are located bilaterally around the midline at the level of the traversing rootlets of the abducens nerve in the pontine brainstem forming the nucleus raphe interpositus (RIP). Healthy OPNs are previously characterized by dense perineuronal net (PN) ensheathment, parvalbumin (PAV) and voltage-gated potassium channel Kv1.1 and Kv3.1 expression. Motivation: The ion channel and transmitter profile of OPNs in human has not been established. The further characterization of OPNs should allow for local delineation of OPNs from other types of neurons found in RIP, as well as identifying potential markers for eye movement disorders such as opsoclonus myoclonus syndrome. Methods: Double immunoperoxidase based-stainings of transverse pontine sections containing human RIP for aggrecan (ACAN) and non-phosphorylated neurofilaments (SMI32) was used to identify OPNs. In consecutive thin paraffin sections, stainings using antibodies against low voltage-activated ion channels (HCN, Cav3) and transmitter related proteins were performed. Results: A separate but morphologically similar population to OPNs was identified around the midline at the same level as OPNs in human pontine sections. This population was cholinergic, lacked PNs, but was labeled by SMI32. Further examination revealed that OPNs and cholinergic non-OPN populations differ in their ion channel (Kv3.1, HCN1-2, Cav3.2) and transmitter related protein (GABRA, GAD, GlyR, vGlut, GluR) expression. Conclusion: OPNs and cholinergic non-OPNs are located intermingled within the traditionally identified RIP, however they expressed distinct histochemical signatures from OPNs. Although the functional significance of the cholinergic non-OPN population in human brainstem is unclear, these findings suggest important distinguishing features that could be missed in histopathological examinations of post-mortem cases with saccadic disorders.
Keywords: High-voltage-gated potassium channels, Low-voltage activated calcium channels, Glutamate, GABA, Glycine
Received: 21 Jul 2025; Accepted: 07 Nov 2025.
Copyright: © 2025 Mayadali, John, Abspacher, Schmitz, Shaikh and Horn. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Anja Kerstin Ellen Horn, anja.bochtler@med.uni-muenchen.de
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