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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 -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:
-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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