Exocytosis and nerve terminal pseudopodia.

When exocytosis of synaptic vesicles is accompanied by the accumulation of vesicle membrane in the nerve terminal membrane, the geometric shape of the terminal must alter. The details of these rearrangements vary with the anatomical site; this laboratory has reported on the responses of abutted nerve terminals in the electric ray electric organ. When they are stimulated so as to lose synaptic vesicles, they develop reciprocal pseudopodial indentations (PSIs) with each other. Assuming that direct abutment of the interacting nerve terminals was necessary for this to occur, we have examined various nuclei of the rat brain limbic system for similar configurations. PSIs are most abundant between abutted terminals synapsing with smooth dendrites in the globus pallidus and substantia nigra. In these locations, there is good reason to believe that they are forming between swellings of the gamma-aminobutyric acid (GABA) afferents from the caudate-putamen. Conservative calculations of the potential accumulation of extracellular K released by action potentials at the PSI tip suggest that 15 mM concentrations could occur at firing rates of 150 Hz. Inasmuch as the GABA projection system to these nuclei is a system of boutons en passant, in which the safety factor for action potential conduction is low, it is suggested that the formation of PSI and the frequency-dependent accumulation of K could lower the safety factor to the point of action potential block. This may affect the inhibitory tone in the substantia nigra. An understanding of how PSI generation is regulated depends in part on knowing what options are available for synaptic vesicle behavior at the moment of depolarization of a nerve terminal. In particular, we need to know whether vesicles can open and close in situ during slow firing under physiological conditions. Recent experimental results enable us to foresee how this could be tested, and the experimental design is described.