Basal ganglia neurons in healthy and parkinsonian primates generate recurring sequences of spikes

The spiking activity of basal ganglia neurons can be characterized by summary statistics such as the average firing rate, or by measures of firing patterns, such as burst discharges, or oscillatory fluctuations of firing rates. Many of these features are altered by the presence of parkinsonism. This study examined another distinct attribute of firing activity, i.e., the occurrence of repeating sequences of interspike intervals (ISIs). We studied this feature in extracellular electrophysiological recordings that were made in the basal ganglia of rhesus monkeys, before and after they had been rendered parkinsonian by treatment with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Neurons in both pallidal segments and in the subthalamic nucleus tended to fire in repeating sequences, typically two ISIs long (i.e., involving three spikes). In recordings that were 5,000 interspike intervals long, 20%–40% of spikes participated in one of many sequences with each ISI replicating the sequence pattern with a timing error of ≤1%. Compared with similar analyses in shuffled representations of the same data, sequences were more common in the original representation of ISIs in all of the tested structures. Induction of parkinsonism reduced the proportion of sequence spikes in the external pallidum but increased it in the subthalamic nucleus. We found no relation between the sequence generation and the firing rate of neurons, and, at most, a weak correlation between sequence generation and the incidence of bursts. We conclude that basal ganglia neurons fire in recognizable sequences of ISIs, whose incidence is influenced by the induction of parkinsonism. NEW & NOTEWORTHY Previous work has shown that the timing of the electrical activity of basal ganglia neurons has nonstochastic properties, resulting in oscillatory firing patterns, or bursting. This article describes another such property in the monkey brain; a surprisingly large proportion of action potentials generated by cells in the extrastriatal basal ganglia are part of precisely timed recurring sequences of spiking events. We also found that the generation of these sequences changes substantially in the parkinsonian state.