Temporal Variability in the Spiking Activity of Neurons in the External Globus Pallidus in Healthy and Parkinsonian Monkeys

The external segment of the globus pallidus (GPe) is a critical node within the indirect pathway of the basal ganglia. In vivo recordings in primates and other animals have shown that most GPe neurons exhibit high frequency firing with pauses, whereas others display low frequency firing with frequent bursts. Although these two firing patterns have been considered to represent distinct neuronal subtypes, evidence suggests that they may instead reflect extremes of a continuous spectrum of firing patterns and rates within this structure. Using long-duration electrophysiologic single unit recordings (5-60 minutes) in awake rhesus macaques (4 females, 3 males), we found that the firing rates and patterns of individual GPe neurons vary substantially over time. In parkinsonian monkeys, GPe neurons continued to show significant variability in firing, although within a more constrained range. Given the temporal fluctuations, long recording durations are necessary to accurately represent the range of firing characteristics of GPe neurons, both in healthy and parkinsonian states. Most GPe cells displayed, at different time points, characteristics of high frequency or low frequency firing modes, but for most of the time fired in an undetermined mode. We conclude that the firing of GPe neurons transition along the extremes of a continuous spectrum of properties, and therefore GPe cells cannot be classified based solely on firing patterns in in vivo recordings. Significance Statement The external globus pallidus (GPe) is a key modulator of basal ganglia activity, influencing movement in health and disease. Classic studies in monkeys categorized GPe neurons into two main types based on their firing patterns. We show that most GPe neurons exhibit substantial variability in firing over minutes, calling into question whether firing patterns alone can reliably define cell types. In parkinsonian monkeys, the firing variability persists. These findings underscore the need for long-duration recordings to capture the dynamic nature of GPe activity and suggest that disease states may constrain this variability, offering new insight into the alteration of the activity of basal ganglia neurons in the parkinsonian state.