Variability and directionality of inferior olive neuron dendrites revealed by detailed 3D characterization of an extensive morphological library

Abstract

The inferior olive (IO) is an evolutionarily conserved brain stem structure and its output activity plays a major role in the cerebellar computation necessary for controlling the temporal accuracy of motor behavior. The precise timing and synchronization of IO network activity has been attributed to the dendro-dendritic gap junctions mediating electrical coupling within the IO nucleus. Thus, the dendritic morphology and spatial arrangement of IO neurons governs how synchronized activity emerges in this nucleus. To date, IO neuron structural properties have been characterized in few studies and with small numbers of neurons; these investigations have described IO neurons as belonging to two morphologically distinct types, “curly” and “straight”. In this work we collect a large number of individual IO neuron morphologies visualized using different labeling techniques and present a thorough examination of their morphological properties and spatial arrangement within the olivary neuropil. Our results show that the extensive heterogeneity in IO neuron dendritic morphologies occupies a continuous range between the classically described “curly” and “straight” types, and that this continuum is well represented by a relatively simple measure of “straightness”. Furthermore, we find that IO neuron dendritic trees are often directionally oriented. Combined with an examination of cell body density distributions and dendritic orientation of adjacent IO neurons, our results suggest that the IO network may be organized into groups of densely coupled neurons interspersed with areas of weaker coupling. Electronic supplementary material The online version of this article (10.1007/s00429-019-01859-z) contains supplementary material, which is available to authorized users.

Imaging Subthreshold Voltage Oscillation With Cellular Resolution in the Inferior Olive in vitro

“…Cluster sizes were similar between D0 and D7 samples (8.3 ± 0.4 and 8 ± 0.5 pixels, corresponding to 20507 square µm and 21868 square µm areas for D0 and D7, respectively; t = 0.43, p = 0.66). These characteristics are in line with previously-reported reconstructions of IO cells (Rekling et al, 2012;Kølvraa et al, 2014;Vrieler et al, 2019).…”

Role of cerebellar GABAergic dysfunctions in the origins of essential tremor

“…However, the interaction between ION and NO neurons involves additional connections, such as the projections from climbing fibers to NO neurons (73), which are currently neglected in our model and may contribute a negative feedback to the ION neurons. In addition, the specific localization of the NO synapses on the ION neurons and the morphology of the dendrites of ION neurons may significantly steer the synchronization within the inferior olivary nucleus (72,(74)(75)(76). Accordingly, it is plausible that the NO-ION connectivity may affect the network oscillations.…”

Quasiperiodic rhythms of the inferior olive

“…It has been shown that in the anesthetized state both the amplitude and phase of the STOs can be altered by synaptic inputs [10]. Inhibitory inputs to the inferior olive originate in the cerebellar nuclei and have broadly distributed terminals onto compact sets of olivary cells [51–53]. Excitatory terminals predominantly originate in the spinal cord and lower brainstem, mainly carrying sensory information, and in the nuclei of the meso-diencephalic junction in the higher brainstem, carrying higher-order input from the cerebral cortex (Fig 1A) [15, 54, 55].…”