Transmitter and ion channel profiles of neurons in the primate abducens and trochlear nuclei

Ümit Suat Mayadali,Jérome Fleuriet,Michael Mustari,Hans Straka,Anja Kerstin Ellen Horn

doi:10.1007/s00429-021-02315-7

Abstract

Extraocular motoneurons initiate dynamically different eye movements, including saccades, smooth pursuit and vestibulo-ocular reflexes. These motoneurons subdivide into two main types based on the structure of the neuro-muscular interface: motoneurons of singly-innervated (SIF), and motoneurons of multiply-innervated muscle fibers (MIF). SIF motoneurons are thought to provoke strong and brief/fast muscle contractions, whereas MIF motoneurons initiate prolonged, slow contractions. While relevant for adequate functionality, transmitter and ion channel profiles associated with the morpho-physiological differences between these motoneuron types, have not been elucidated so far. This prompted us to investigate the expression of voltage-gated potassium, sodium and calcium ion channels (Kv1.1, Kv3.1b, Nav1.6, Cav3.1–3.3, KCC2), the transmitter profiles of their presynaptic terminals (vGlut1 and 2, GlyT2 and GAD) and transmitter receptors (GluR2/3, NMDAR1, GlyR1α) using immunohistochemical analyses of abducens and trochlear motoneurons and of abducens internuclear neurons (INTs) in macaque monkeys. The main findings were: (1) MIF and SIF motoneurons express unique voltage-gated ion channel profiles, respectively, likely accounting for differences in intrinsic membrane properties. (2) Presynaptic glutamatergic synapses utilize vGlut2, but not vGlut1. (3) Trochlear motoneurons receive GABAergic inputs, abducens neurons receive both GABAergic and glycinergic inputs. (4) Synaptic densities differ between MIF and SIF motoneurons, with MIF motoneurons receiving fewer terminals. (5) Glutamatergic receptor subtypes differ between MIF and SIF motoneurons. While NMDAR1 is intensely expressed in INTs, MIF motoneurons lack this receptor subtype entirely. The obtained cell-type-specific transmitter and conductance profiles illuminate the structural substrates responsible for differential contributions of neurons in the abducens and trochlear nuclei to eye movements.

Highlights

Extraocular muscles and innervation by motoneurons in the abducens and trochlear nuclei Extraocular muscles are responsible for diverse types of eye movements including saccades, smooth pursuit, vestibuloocular and optokinetic reflexes, and for fixation (Leigh and Zee 2015)
Using cell types determined by choline acetyltransferase (ChAT) and ACAN staining (Fig. 7a–c, right), we found that while glycine transporter 2 (GlyT2)-immunopositive puncta were present to a comparable extent along the somatic membrane of SIF motoneurons and internuclear neurons (INTs) in the abducens nucleus (Fig. 7c, left column; green arrows and blue arrows, respectively), considerably fewer puncta were observed along the somatic membrane of MIF motoneurons (Fig. 7b, left column, red arrowheads)
This study explored the basis for the functional properties of different groups of neurons in the abducens and trochlear nuclei in macaque monkey using immunohistochemistry with an emphasis on motoneurons of MIF and SIF muscle fibers, as shown in the summary figure (Fig. 10)

Summary

Introduction

Extraocular muscles and innervation by motoneurons in the abducens and trochlear nuclei Extraocular muscles are responsible for diverse types of eye movements including saccades, smooth pursuit, vestibuloocular and optokinetic reflexes, and for fixation (Leigh and Zee 2015). MIFs are associated with another type of nerve terminal, the palisade endings, which are located at the proximal and distal myotendinous junctions. Whether these unique eye muscle specializations have a sensory or motor function is still being debated (Lienbacher and Horn 2012; Zimmermann et al 2013). Eye movements result from coordinated contractions of largely synergistic extraocular muscles through task-specific cooperation by MIFs and SIFs. For horizontal eye movements, lateral rectus muscles are activated by motoneurons in the ipsilateral abducens nucleus (nVI), located in the hindbrain pontine tegmentum; and for vertical and torsional eye movements, by motoneurons in the oculomotor (nIII) and trochlear (nIV) nuclei located in the mesencephalon and rostral hindbrain, respectively (Horn and Straka 2021). PMT neurons presumably send an efference copy of premotor commands to the cerebellar floccular region (Büttner-Ennever 1992; Horn et al 2018)

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