Faculty Bibliography

Specific chemical lesion of the rat inferior olive by intraperitoneal administration of 3-acetylpyridine prevents recuperation from motor abnormalities generated by unilateral labyrinthine lesion. Moreover, in animals that have recuperated from the balyrinthine lesion, 3-acetylpyridine produces a reversal of the symptoms within 2 hours of administration. These results indicate that the integrity of the olivo-cerebellar system is necessary for the acquisition and retention of this form of motor learning, but that the cerebellum itself is not the seat of such learning.

The innervated and noninnervated membranes of Torpedo electrocytes have been examined by electron microscopy of thin-sectioned and freeze-fractured specimens. The ventral innervated membrane is approximately 120 A thick and is characterized by an unusually broad outer dense lamina (approximately 60 A) in which a granular substructure can be resolved. The granules are approximately 70 A in diameter and are spaced irregularly. The same membrane specialization was noted in a previous study of amphibian myoneural junctions, and it was proposed then that the granular elements represent ACh receptor molecules. The morphologically equivalent structures presumably have the same significance in the Torpedo electric organ. However, in this case the specialized membrane covers the entire innervated surface, leading to the conclusion that high concentrations of receptors occur normally in extrajunctional as well as post-junctional regions of the innervated membrane of the electrocyte. In replicas of freeze-fractured specimens, the A face of this membrane is covered with large particles having the same distribution and approximate concentration as the granules visible in thin sections, indicating that the granules visible at the outer surface of the membrane extend at least into the hydrophobic middle layer of the membrane. The cytoplasmic surface of this membrane has an amorphous coating into which 'decorated' cytoplasmic filaments insert. Synaptic vesicle and axon terminal membranes also contain granules visible in thin sections but with a much sparser distribution. These probably correspond to the intramembranous particles seen in freeze-fractured specimens. Vesicles are occasionally attached to the axolemma by thin linear strands.

A Leptomonas of insect origin was highly susceptible to several standard trypanocides and leishmanicides in vitro. Resistance was induced to some of these drugs; clones were isolated from each strain. Cross-resistance patterns of the clones were derived for diamidines, quinapyramine (Antrycide), acriflavin, phenanthridines, and other drugs active against trypanosomes and leishmanias. Clones tested included two each that were resistant to acriflavin, Antrycide, diminazene aceturate (Berenil), and pentamidine and one that was resistant to stilbamidine. Appreciable cross-resistance was evident for all clones. Differences were observed between clones from the same parent strain. Collateral susceptibility towards isometamidium and oxophenarsine was detected in most clone-derived populations. In clones passaged without drug to test for drug fastness, acriflavin and pentamidine clones lost resistance within 10 transfers, whereas Berenil and Antrycide clones retained considerable resistance after 20 to 30 subcultures without drug. Considerations of differences in life cycles suggest that the clone collection may be useful in screening for agents effective against leishmanias and stercorarian trypanosomes rather than against salivary trypanosomes.