Coinciding Decreases in Discharge Rate Suggest That Spontaneous Pauses in Firing of External Pallidum Neurons Are Network Driven

Abstract

The external segment of the globus pallidus (GPe) is one of the core nuclei of the basal ganglia, playing a major role in normal control of behavior and in the pathophysiology of basal ganglia-related disorders such as Parkinson's disease. In vivo, most neurons in the GPe are characterized by high firing rates (50 -100 spikes/s), interspersed with long periods (ϳ0.6 s) of complete silence, which are termed GPe pauses. Previous physiological studies of single and pairs of GPe neurons have failed to fully disclose the physiological process by which these pauses originate. We examined 1001 simultaneously recorded pairs of high-frequency discharge GPe cells recorded from four monkeys during task-irrelevant periods, considering the activity in one cell while the other is pausing. We found that pauses (n ϭ 137,278 pauses) coincide with a small yet significant reduction in firing rate (0.78 Ϯ 0.136 spikes/s) in other GPe cells. Additionally, we found an increase in the probability of the simultaneously recorded cell to pause during the pause period of the "trigger" cell. Importantly, this increase in the probability to pause at the same time does not account for the reduction in firing rate by itself. Modeling of GPe cells as class 2 excitability neurons (Hodgkin, 1948) with common external inputs can explain our results. We suggest that common inputs decrease the GPe discharge rate and lead to a bifurcation phenomenon (pause) in some of the GPe neurons.

Hold your pauses: external globus pallidus neurons respond to behavioural events by decreasing pause activity

“…On the other hand, previous pairwise correlation of simultaneously recorded GPe neurons failed to find pause‐to‐pause and pause‐to‐spike correlations, suggesting an intrinsic phenomenon (Elias et al ., ). These conflicting results may be explained by a recent study of our group (Schechtman et al ., ) that employed population analysis, which is more sensitive than pairwise correlation analysis. This population analysis revealed a small (1–2 spikes/s) decrease in the GPe discharge rate coincident with GPe pauses, suggesting that pauses reflect the interplay between common network inhibition and intrinsic cellular properties of GPe neurons.…”

The external globus pallidus: progress and perspectives

“…Such an anatomical organization allows dStr axons to contact the dendrites of multiple GPe neurons. The sharing of dStr inputs by multiple GPe neurons provides an anatomical substrate for synchrony and pause‐burst firing pattern in a large population of GPe neurons, as demonstrated by both experimental and computational studies (Terman et al ., ; Elias et al ., ; Zold et al ., ,b; Kita & Kita, ,b; Adler et al ., ; Schwab et al ., ; Wilson, ; Schechtman et al ., ). As PD progresses, the activity of GPe neurons transitions from decorrelated, single‐spike pacemaking to synchronous, rhythmic bursting (but see Mallet et al ., ).…”

Ethanol-Sensitive Pacemaker Neurons in the Mouse External Globus Pallidus

“…Interestingly, in humans, ethanol appears to decrease GPe activity, as evidenced by neuroimaging studies in which an oral dose of ethanol dampened the increase of GPe activity during a visual task and induced a slight decrease of GPe activity ( Nikolaou et al , 2013 ). Although we are aware that GPe high-frequency neurons are characterized by interspersed pauses in monkeys ( DeLong, 1971 ; Elias et al , 2007 ; Noblejas et al , 2015 ; Schechtman et al , 2015 ), we observed only occasional pausing behavior in some GPe neurons (data not shown). One reason for this difference may be species, as in rodents it has been reported that a subset of high-frequency neurons showed only occasional brief pauses ( Dodson et al , 2015 ; Mallet et al , 2016 ).…”