Do silent dopaminergic neurons exist in rat substantia nigra in vivo?

A subpopulation of inactive or "silent" dopaminergic neurons has been reported to exist in vivo in rat substantia nigra, comprising up to 50% of nigral dopaminergic neurons. The existence of this large proportion of silent neurons has been inferred from various experimental manipulations, but never demonstrated directly. In the present study, striatal or medial forebrain bundle stimulation was used to activate antidromically substantia nigra dopaminergic neurons in vivo. Antidromic spikes of dopaminergic neurons observed by extracellular single-unit recordings in the absence of spontaneous activity were employed as indicators of the presence of a silent cell. A total of 312 dopamine neurons were recorded, including 190 neurons that could be antidromically activated from the striatum and/or the medial forebrain bundle. All neurons exhibited spontaneous activity. The firing rates were unimodally distributed about the mean of 4 spikes/s, and very few cells were observed to fire at less than 0.5 spikes/s. The numbers of spontaneously active and antidromically activated dopaminergic neurons per track were recorded and compared with the number of antidromically responding silent dopaminergic neurons per track after systemic apomorphine administration. Under control conditions, 0.80 +/- 0.10 or 1.36 +/- 0.13 spontaneously active neurons per track could be antidromically activated at 1.0 mA by striatal or medial forebrain bundle stimulation, respectively. After apomorphine completely suppressed spontaneous activity, 0.69 +/- 0.08 and 1.39 +/- 0.14 antidromic neurons per track were detected by stimulating the striatum or medial forebrain bundle respectively at 1.0 mA, demonstrating that silent dopaminergic neurons can be reliably identified through antidromic activation. In sharp contrast to previous reports, these data suggest that silent neurons do not comprise a substantial proportion of the total number of dopaminergic neurons in the substantia nigra. Reverse chi(2) analysis revealed that, if they exist at all, silent dopaminergic neurons make up less than 2% of the dopaminergic cells in the substantia nigra. These findings are related to current theories of the mechanisms of action of antipsychotic drugs and the maintenance of near-normal levels of dopamine in the striatum following large-scale loss of nigral dopaminergic neurons. (C) 1998 IBRO. Published by Elsevier Science Ltd.