Structure and function of gustatory neurons in the nucleus of the solitary tract. IV. The morphology and synaptology of GABA-immunoreactive terminals.

In the visual, auditory and somatosensory systems, insight into the synaptic arrangements of specific types of neurons has proven useful in understanding how sensory processing within that system occurs. The neurotransmitter GABA is present in the nucleus of the solitary tract and based on the fact that the vast majority of cells respond to GABA, its agonists and antagonists, and that over 45% of synaptic terminals in the rostral subdivision of the nucleus of the solitary tract are GABA-immunoreactive, GABA is thought to play an important role in gustatory processing. The following study was carried out to establish the distribution of GABA-immunoreactive terminals within the nucleus of the solitary tract. Specifically, the distribution on to physiologically-identified gustatory neurons was determined using post-embedding electron immuno-histochemistry. GABA-immunoreactive terminals synapse with gustatory neuronal somata and all portions of their dendrites, but non-GABAergic terminals synapse only with distal dendrites of the gustatory cells and on to correspondingly small unidentified dendritic profiles in the neuropil. There is a differential distribution of two subtypes of GABA-immunoreactive terminals on to proximal and distal portions of the gustatory neurons as well. Finally, a model for the synaptic arrangements involving gustatory and GABAergic neurons is proposed.

Structure and function of gustatory neurons in the nucleus of the solitary tract. III. Classification of terminals using cluster analysis.

In sensory systems, insight into synaptic arrangements on cells of known physiological response properties has helped our understanding of the structural basis for these properties. To carry out these types of studies, however, synaptic types in the region of interest must be defined. Unfortunately, defining synaptic types in the brainstem has proved to be a challenging enterprise. Our study was done to classify synapses in the gustatory part of the nucleus solitarius using objective quantitative criteria and a cluster analysis procedure. Cluster analysis allows classification of a population of objects, such as synaptic terminals, into groups that exhibit similar characteristics. Six terminal types were identified using cluster analysis and subsequent analyses of variance and post hoc tests. Unlike classification schemes used for the cerebral cortex, where synaptic apposition density thickness and shape of vesicles is useful (Gray's Type I and II synapses), the concentration of vesicles in a terminal was a more useful measurement with which to classify terminals in the nucleus solitarius. To validate that vesicle density (vesicles/microm2) is a useful defining characteristic to classify terminals in the nucleus solitarius, terminals of a known type were used. GABAergic terminals were identified using postembedding immunohistochemical techniques, and their vesicle density was determined. GABAergic terminals fall into the range of two of the terminal types defined by the cluster analysis and, based on vesicle density, two types of GABAergic terminals were identified. We conclude that vesicle density is a helpful means to identify synapses in this brainstem nucleus.

Modulation of [3H]quinpirole binding in brain by monoamine oxidase inhibitors: evidence for a potential novel binding site.

[3H]Quinpirole is a dopamine agonist with high affinity for the D2 and D3 dopamine receptor subtypes. A variety of drugs, most notably monoamine oxidase inhibitors (MAOls), inhibit the binding of [3H]quinpirole, but not [3H]spiperone or [3H](-)N-n-Propylnorapomorphine, in rat striatal membranes by a mechanism that does not appear to involve the enzymatic activity of MAO. This study extends the characterization of MAOI-displaceable [3H]quinpirole binding in rat brain. Clinically antidepressant MAOIs exhibited selectivity between sites labeled by [3H]quinpirole and [3H]spiperone as did a number of structurally related propargylamines and N-acylethylenediamine derivatives and other drugs such as debrisoquin and phenylbiguanide. The MAOIs clorgyline and Ro 41-1049 were the most potent. Anti-depressant MAOIs inhibited [3H]quinpirole binding with the following rank order of potency: phenelzine > pargyline > tranyl-cypromine > isocarboxazid > nialamide > moclobemide. In striatal membranes, MAOI Ro 41-1049 inhibited [3H]quinpirole binding with similar potency at a variety of incubation temperatures (4-37 degrees C), assay tissue concentrations (5-20 mg original wet weight/ml), and time points (2 min-4 hr) and in the presence or absence of K+, Mg2+, Ca2+ ions, ascorbate, EDTA and NaCl. The regional distribution of Ro 41-1049-displaceable [3H]quinpirole binding in brain paralleled that of D2-like receptors. These data suggest that MAOIs interact with a novel binding site that is labeled by [3H]quinpirole or that modulates [3H]quinpirole binding. This site may be associated with D2-like dopamine receptors.