Oscillation of interspike interval length in substantia nigra dopamine neurons: effects of nicotine and the dopaminergic D2 agonist LY 163502 on electrophysiological activity.

Abstract

The rates and patterns of discharge activity exhibited by 16 spontaneously active substantia nigra pars compacta dopamine neurons were studied in halothane-anesthetized rats using three types of quantitative measures: 1) mean discharge rates, 2) population characteristics of interspike interval samples, and 3) interspike interval time-series measures which were used to examine patterns in the ordering of interspike intervals. The mean discharge rate of these 16 cells was 2.9 +/- 0.3 spikes/sec, and each cell was classified as bursting (25% of the cells) or non-bursting (75%). The distribution of interspike intervals of non-bursting neurons were more normally distributed. Time-series analyses (raw time-series plots, return maps, and phase portraits) revealed a substantial oscillatory tendency in the magnitudes of consecutive interspike intervals in these neurons under baseline conditions: Successive interspike intervals tended to alternate between short and long durations, although short bursts often occurred. Under baseline conditions, these cells exhibited both multispike bursts and consecutive long intervals less frequently than would have been predicted by chance ordering of the interspike intervals. These results imply that there are mechanisms acting to reduce the probability of these types of events. Locally infused nicotine enhanced discharge rates in these neurons. Burst firing increased in four neurons, while five neurons did not show any change in burst firing. LY 163502 induced significant decreases in both discharge rate and bursting activity in all cells tested. The variation coefficient, skew, and kurtosis of the interspike interval distributions were not consistently altered by either drug. The local infusion of either nicotine or LY 163502 decreased the oscillatory phenomenon seen in the baseline condition. Neither the nicotine or LY 163502 time-series data exhibited a larger proportion of long-short and short-long pairs (relative to the median interval) than would be expected by chance. It is hypothesized that these neurons have intrinsic mechanisms, made manifest under anesthesia, which induce oscillations in interspike interval length. The oscillatory effect of these mechanisms can be overridden by tonic increases in either excitatory or inhibitory tone.