Localization of glutamic-acid-decarboxylase-immunoreactive axon terminals in the inferior olive of the rat, with special emphasis on anatomical relations between GABAergic synapses and dendrodendritic gap junctions.
Immunocytochemical and electron microscopic methods were used to examine the GABAergic innervation of the inferior olivary nucleus in adult rats. This neuronal system was visualized with an antibody against glutamic acid decarboxylase (GAD, EC 4.1.1.15), the GABA-synthesizing enzyme. A GAD-positive reaction product was encountered only in short segments of preterminal axons and in axon terminals. Their relative number per unit area of neuropil was very similar in all olivary subnuclei. Despite this homogeneity in density, obvious intraregional differences existed. Some regions were strongly immunoreactive (the "c" subgroup, the beta nucleus, and the mediolateral outgrowth of the medial accessory olive), whereas others were weakly labeled (the dorsomedial cell column and the central zones of the medial accessory and principal olives). The strongly immunoreactive areas contained the largest and most intensively labeled axon terminals. Areas of weak labeling were filled with small, weakly immunoreactive nerve terminals. Thus, variations in size and in intensity of labeling create a specific pattern of GABA innervation, revealed by an almost continuous gradient between the above-mentioned extremes. The GAD-positive axon terminals established conventional synapses with dendrites (94% of the samples) or with cell bodies (6%). The vast majority of these synapses were type II (84%) and only a small proportion formed type I synaptic contacts (16%), regardless of the nature of the postsynaptic element. Immunoreactive terminals were also involved in the complex synaptic arrangements--the glomeruli, which characterize the olivary neuropil. Within these formations, olivary neurons were electrotonically coupled through dendrodendritic gap junctions. There was a constant association between GAD-positive axon terminals and small dendritic appendages linked by gap junctions. This association was revealed not only by the systematic presence of immunolabeled terminals directly apposed to the dendritic appendages but, more importantly, by the frequent presence of type II synapses straddling both elements. These synapses were in close proximity to the low-resistance pathways represented by the gap junctions. The strategic location of these GABA synapses is discussed in relation to recent findings indicating the possibility of a synaptic modulation of the electrical coupling: the release of GABA, by increasing nonjunctional membrane conductance, could shunt the coupling between olivary neurons. The functional decoupling of selected gap junctions would be responsible for the spatial organization of the olivary electrotonic coupling.
D000818:Animals; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D008297:Male; D009847:Olivary Nucleus / Q000201:enzymology* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013569:Synapses / Q000648:ultrastructure; D009435:Synaptic Transmission; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase