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The Journal of Neuroscience, June 1, 1998, 18(11):4106-4118

Presynaptic Recording of Quanta from Midbrain Dopamine Neurons and Modulation of the Quantal Size

Emmanuel N. Pothos, Viviana Davila, and David Sulzer

Departments of Neurology and Psychiatry, Columbia University, New York, New York 10032, and Department of Neuroscience, New York State Psychiatric Institute, New York, New York 10032

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 predominantly contain small synaptic vesicles. Quantal events were elicited by high K+ or alpha -latrotoxin, required extracellular Ca2+, and were abolished by reserpine. The events indicated the release of 3000 molecules over 200 µsec, much smaller and faster events than quanta associated with large dense-core vesicles previously recorded in vertebrate preparations. The number of dopamine molecules per quantum increased as a population to 380% of controls after glial-derived neurotrophic factor (GDNF) exposure and to 350% of controls after exposure to the dopamine precursor L-dihydroxyphenylalanine (L-DOPA). These results introduce a means to measure directly the number of transmitter molecules released from small synaptic vesicles of CNS neurons. Moreover, quantal size was not an invariant parameter in CNS neurons but could be modulated by neurotrophic factors and altered neurotransmitter synthesis.

Key words: alpha -latrotoxin; amperometry; dopamine; electrochemistry; exocytosis; GDNF; L-DOPA; midbrain; quantal analysis; quantal release; recycling; synaptic vesicles; VMAT


Copyright © 1998 Society for Neuroscience  0270-6474/98/18114106-13$05.00/0


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