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

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.

Saccadic premotor burst neurons and histochemical correlates of their firing patterns in rhesus monkey

“…3c; gray arrows), and may therefore represent the tonic neurons with eye position sensitivity described in squirrel monkey [54]. This assumption would be in line with the recently observed differential histochemical characteristics of MIF and SIF motoneurons [43]. The former population lacks PN and Kv3.1, and expresses reduced Kv1.1, compared to PNpositive SIF motoneurons with strong Kv1.1 and Kv3.1b expression.…”

“…Furthermore, via gene-profiling, the authors identified a strong correlation between fast-firing and Kv1.1, Kv3.1 (and Nav1.6) co-expression [37]. This co-expression profile was already observed in the neurons of oculomotor circuitry, such as omnipause neurons (OPNs) [42], pre-oculomotor (dorsal) Y-group neurons [73], and SIF motoneurons within the abducens and trochlear nuclei, as well as the internuclear neurons of the abducens nucleus [43]. Therefore, with the addition of results regarding premotor burst neurons presented in this study, there's significant evidence that the tightly controlled and rapid eye movement types require simultaneous expression of Kv1.1 and Kv3.1 at multiple levels in the oculomotor circuitry.…”

“…Our recent work has found significant differences between the ion channel profiles of MIF and SIF motoneurons in the abducens and trochlear nuclei [43]. MIF motoneurons, which are considered to be responsible for low-dynamic motor commands, had reduced Kv1.1 levels, and no membrane bound Kv3.1, in comparison to SIF motoneurons, which strongly expressed Kv1.1 and Kv3.1 subunit immunoreactivity [43].…”

“…The former population lacks PN and Kv3.1, and expresses reduced Kv1.1, compared to PNpositive SIF motoneurons with strong Kv1.1 and Kv3.1b expression. It is likely that this reflects the different firing characteristics expressed by these motoneuron populations [6,21,43]. Additionally, expression of CR in itself could be related to excitability [16,40,53].…”

MIF versus SIF Motoneurons, What Are Their Respective Contribution in the Oculomotor Medial Rectus Pool?

“…However, a full exploration of frequencies and amplitudes of stimulation is required to further ascertain the differences in the dynamics of MIF and SIF motoneurons. The vestibulo-ocular pathways manifest differential adaptation properties based on their frequency selectivity (Lisberger et al, 1983), thus it is possible that these separate channels (i.e., low vs high frequency) extend to the motoneurons (Dietrich et al, 2017) and that intrinsic membrane properties along vestibular neurons and motoneurons are tuned to determine the firing and discharge properties of MIF and SIF motoneurons (Serafin et al, 1991a,b;Nieto-Gonzalez et al, 2007;Mayadali et al, 2021). Altogether, it can be suggested that individual extraocular motoneurons do not specialize in producing selectively any of the different types of eye movements (see, however, Henn and Cohen, 1972).…”