Anatomy and Embryology

, Volume 184, Issue 3, pp 225–243

The GABAergic cerebello-olivary projection in the rat

  • Barbara J. Fredette
  • Enrico Mugnaini
Article

DOI: 10.1007/BF01673258

Cite this article as:
Fredette, B.J. & Mugnaini, E. Anat Embryol (1991) 184: 225. doi:10.1007/BF01673258

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.

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

Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • Barbara J. Fredette
    • 1
  • Enrico Mugnaini
    • 1
  1. 1.Laboratory of NeuromorphologyUniversity of ConnecticutStorrsUSA
  2. 2.Department of Physiology and Neurobiology, U-42University of ConnecticutStorrsUSA