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The GABAergic cerebello-olivary projection in the rat

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Summary

Immunocytochemical detection of glutamate decarboxylase (GAD), the predominant biosynthetic enzyme of gamma-aminobutyric acid (GABA), reveals the presence of a dense GABAergic innervation in all parts of the inferior olive. One brain center that provides a substantial projection to the inferior olive is the cerebellar nuclei, which contain many small GABAergic neurons. These neurons were tested as a source of GABAergic olivary afferents by combining retrograde tract tracing with GAD immunocytochemistry. As expected from previous studies, injections of wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) into the inferior olive retrogradely label many small neurons in the interposed and lateral cerebellar nuclei and the dorsal part of the lateral vestibular nucleus, and fewer neurons in the ventro-lateral region of the medial cerebellar nucleus. These projections are predominantly crossed and are topographically arranged. The vast majority, if not all, of these projection neurons are also GAD-positive. The relative contribution of this projection to the GABAergic innervation of the inferior olive was tested by lesion of the cerebellar nuclei, or the superior cerebellar peduncle. Within 10 days the lesion eliminates most GAD-immunoreactive boutons in the principal olive, the rostral lamella of the medial accessory olive, the ventrolateral outgrowth, and the lateral part of the dorsal accessory olive ventral fold. Thus, the effectiveness of this depletion demonstrates that the cerebellar nuclei provide most of the GABAergic innervation to regions of the inferior olive known to receive a cerebellar projection. Moreover, when the lateral vestibular nucleus is damaged, the dorsal fold of the dorsal accessory olive is depleted of GABAergic boutons. The synaptic relations that boutons of the GABAergic cerebello-olivary projection share with olivary neurons were investigated at the electron microscopic level by GAD-immunocytochemistry, anterograde degeneration of the cerebellar axons or anterograde transport of WGA-HRP. All of these methods confirm that GABAergic, cerebello-olivary axon terminals contain pleomorphic vesicles, and synapse on various portions of olivary neurons, and especially on dendritic spines within glomeruli, often in very close proximity to the gap junctions that characteristically couple the dendritic profiles. These results demonstrate four major points: that virtually all of the GABAergic, and presumably inhibitory, neurons of the cerebellar and dorsal lateral vestibular nuclei are projection neurons; that a large portion of the inferior olive receives GABAergic afferents from the cerebellar nuclei; that a portion of the dorsal accessory olive receives GABAergic afferents from the dorsal lateral vestibular nucleus; and that cerebello-olivary fibers often synapse near gap junctions, and therefore could influence electrical coupling of olivary neurons.

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Abbreviations

aMAO :

subnucleus a of MAO

beta :

beta nucleus

bMAO :

subnucleus b of MAO

cMAO :

subnucleus c of MAO

dc :

dorsal cap

DC :

dorsal cochlear nucleus

dfDAO :

dorsal fold of DAO

dlh :

dorsal lateral hump of cerebellar nuclei

dIPO :

dorsal lamella of PO

Giαa :

gigantocellular reticular nucleus

dmcc :

dorsomedial cell column

GABA :

gamma-aminobutyric acid

GAD :

glutamate decarboxylase

HRP :

horseradish peroxidase

icp :

inferior cerebellar peduncle

IC :

inferior colliculus

Inf :

infracerebellar nucleus

IntA :

anterior interposed cerebellar nucleus

IntP :

posterior interposed cerebellar nucleus

Lat :

lateral cerebellar nucleus

LRt :

lateral reticular nucleus

LSO :

lateral superior olive

LVe :

lateral vestibular nucleus

MAO :

medial accessory olive

Med :

medial cerebellar nucleus

Me5 :

mesencephalic trigeminal nucleus

MVe :

medial vestibular nucleus

PFl :

paraflocculus of the cerebellar cortex

PO :

principle olive

RMg :

raphe magnus

rMAO :

rostral lamella of MAO

rs :

rubrospinal tract

scp :

superior cerebellar peduncle

SuVe :

spinal vestibular nucleus

SuVe :

superior vestibular nucleus

vfDAO :

ventral fold of DAO

vlo :

ventrolateral outgrowth

vlPO :

ventral lamella of PO

Y :

Y, y vestibular nucleus

WGA :

wheatgerm agglutinin

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  1. Barbara J. Fredette

    Present address: Department of Physiology and Neurobiology, U-42, University of Connecticut, 06269, Storrs, CT, USA

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  1. Laboratory of Neuromorphology, University of Connecticut, Box U-154, 06269, Storrs, CT, USA

    Barbara J. Fredette & Enrico Mugnaini

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  1. Barbara J. Fredette
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This paper is dedicated to Professor Fred Walberg on the occasion of his 70th hirthdav

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Fredette, B.J., Mugnaini, E. The GABAergic cerebello-olivary projection in the rat. Anat Embryol 184, 225–243 (1991). https://doi.org/10.1007/BF01673258

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