Transmitter and ion channel profiles of saccadic omnipause neurons and cholinergic non-omnipause neurons in human nucleus raphe interpositus

Mayadali, Ümit S.; John, Maximilian; Abspacher, Michael; Schmitz, Christoph; Shaikh, Aasef G.; Horn, Anja K. E. (2025): Transmitter and ion channel profiles of saccadic omnipause neurons and cholinergic non-omnipause neurons in human nucleus raphe interpositus. Frontiers in Neuroanatomy, 19: 1670220. ISSN 1662-5129

Abstract

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.

• Dokumententyp: Artikel (LMU)
• Organisationseinheit (Fakultäten): 07 Medizin > Anatomische Anstalt
• DFG-Fachsystematik der Wissenschaftsbereiche: Lebenswissenschaften
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 491502892
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 434691666