DO SILENT DOPAMINERGIC-NEURONS EXIST IN RAT SUBSTANTIA-NIGRA IN-VIVO

A subpopulation of inactive or ''silent'' dopaminergic neurons has bee n reported to exist in vivo in rat substantia nigra, comprising up to 50% of nigral dopaminergic neurons. The existence of this large propor tion of silent neurons has been inferred from various experimental man ipulations, but never demonstrated directly. In the present study, str iatal or medial forebrain bundle stimulation was used to activate anti dromically substantia nigra dopaminergic neurons in vivo. Antidromic s pikes of dopaminergic neurons observed by extracellular single-unit re cordings in the absence of spontaneous activity were employed as indic ators of the presence of a silent cell. A total of 312 dopamine neuron s were recorded, including 190 neurons that could be antidromically ac tivated from the striatum and/or the medial forebrain bundle. All neur ons exhibited spontaneous activity. The firing rates were unimodally d istributed about the mean of 4 spikes/s, and very few cells were obser ved to fire at less than 0.5 spikes/s. The numbers of spontaneously ac tive and antidromically activated dopaminergic neurons per track were recorded and compared with the number of antidromically responding sil ent dopaminergic neurons per track after systemic apomorphine administ ration. Under control conditions, 0.80 +/- 0.10 or 1.36 +/- 0.13 spont aneously active neurons per track could be antidromically activated at 1.0 mA by striatal or medial forebrain bundle stimulation, respective ly. 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 a t 1.0 mA, demonstrating that silent dopaminergic neurons can be reliab ly identified through antidromic activation. In sharp contrast to prev ious 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 drug s and the maintenance of near-normal levels of dopamine in the striatu m following large-scale loss of nigral dopaminergic neurons. (C) 1998 IBRO. Published by Elsevier Science Ltd.