62 Neural Correlates of Cognitive Function in the Basal Ganglia

Abstract

Objective:

Timing, or the decision of when to act, is essential to mammalian behaviors from escaping predators to driving a car. It requires cognitive functions such as working memory for time-based rules and attention to the passing of time. Thus, it can be used as a proxy for higher order executive functions that are difficult to measure but are impaired in many neurological disorders. Therefore, insights from studies of interval timing, tasks which require estimating time intervals of several seconds, have great value for our understanding of human disease. Crucial to timing is the basal ganglia, which integrates cortical activity with midbrain dopamine signals and sends out signals to the spinal cord that regulate movement, motivation, and other behaviors. We have previously found that within the basal ganglia, medium spiny neurons of the striatum exhibit ramping activity in time-related tasks. In other words, they gradually increase or decrease firing frequency across a timed interval, and this is thought to encode time. Yet it is still unknown how the encoding of time is translated into time-based motor responses. To answer this question, we turned to the external globus pallidus (GPe) because it is a regulatory hub within the basal ganglia and is thus well positioned to regulate timing behavior. We sought to examine how the GPe functions in response to time-based demands.

Participants and Methods:

We recorded from neuronal ensembles using 16 channel electrode arrays implanted in the GPe of five mice while they performed an interval timing task called the switch interval timing task. Spike sorting was then used to identify signal from individual neurons.

Results:

Data were compiled from 43 neurons over several trials. Principal component analysis of neural firing activity was then conducted and revealed a downward ramping pattern in GPe neurons during interval timing trials. Data were then separated based on trials in which mice made correct decisions and those in which mice made a mistake. We found that when mice make correct timing decisions, there is downward ramping activity in the GPe, yet when mice make timing mistakes, this ramping pattern is lost.

Conclusions:

Our findings suggest that the GPe processes timing signals through ramping activity, before projecting to the output nuclei of the basal ganglia. This is a novel finding and contributes to a growing understanding of the temporal code of the basal ganglia. The full extent of this code is still unknown, but this insight contributes to a better understanding of how the globus pallidus represents cognition. If we can better explain the neural correlates of timing, we can use this knowledge to inform therapeutic interventions for basal ganglia dysfunction, which could have profound implications for diseases like Parkinson’s disease, which affects millions around the world.