PRESYNAPTIC RECORDING OF QUANTA FROM MIDBRAIN DOPAMINE NEURONS AND MODULATION OF THE QUANTAL SIZE

The observation of quantal release from central catecholamine neurons has proven elusive because of the absence of evoked rapid postsynaptic currents. We adapted amperometric methods to observe quantal release directly from axonal varicosities of midbrain dopamine neurons that pr edominantly contain small synaptic vesicles. Quantal events were elici ted by high K+ or alpha-latrotoxin, required extracellular Ca2+, and w ere abolished by reserpine. The events indicated the release of 3000 m olecules over 200 mu sec, much smaller and faster events than quanta a ssociated with large dense-core vesicles previously recorded in verteb rate preparations. The number of dopamine molecules per quantum increa sed as a population to 380% of controls after glial-derived neurotroph ic factor (GDNF) exposure and to 350% of controls after exposure to th e dopamine precursor L-dihydroxyphenylalanine (I-DOPA). These results introduce a means to measure directly the number of transmitter molecu les released from small synaptic vesicles of CNS neurons. Moreover, qu antal size was not an invariant parameter in CNS neurons but could be modulated by neurotrophic factors and altered neurotransmitter synthes is.