The Motor Thalamus: An Invigorating Hub of Neural Activity

Abstract

The motor thalamus (Mthal) is poised between subcortical and cortical motor structures and is, in the simplest terms, understood as a “relay” for neural activity. However, it is increasingly appreciated that Mthal plays a complex, integrative function. This view is emerging from clinical applications where modifying Mthal activity ameliorates the motor symptoms of several movement disorders, including Parkinson’s disease (PD). Little is understood, however, about how neural signals are integrated by Mthal and how this integration shapes ongoing behavior. Answers to these questions hold important implications for basic science and future therapies of brain disease.

My studies address major questions about Mthal physiology by recording chronic, in vivo electrophysiology in behaving rats. Given the parallels between rodent and human motor circuits, rats are a useful translational model. I leveraged a two-alternative forced choice task where movement is both ballistic and lateralized. I found that Mthal single unit activity (or “spiking”) is greatly enhanced around movement initiation. Importantly I identified units that fired in a manner that was either “directionally selective” or “non-directionally selective”. Using two performance measures, reaction time (RT) and movement time (MT), I also show that Mthal activity is proportional to the speed of movement. Directionally selective units correlate with RT and MT, non-directionally selective units correlate exclusively with RT.

Mthal spiking is known to be correlated with rhythmic oscillations in the extracellular local field potential (LFP). I therefore determined relationships between Mthal unit spiking, behavior and LFP. I discovered that the phase of low frequency oscillations in the delta band (1-4 Hz) predicts spike timing, especially for directionally selective units. Delta phase also predicts RT and aligns to each event, suggesting a role in task timing. The power of higher frequency oscillations, namely beta (13-30 Hz) and low-gamma (30-70 Hz), are nested within the delta phase. Taken together, these results support a model whereby delta phase regulates high-frequency interactions and neuronal excitability in Mthal, which reflects motor performance.

To begin parsing behavioral causality with spatiotemporal precision, I implemented a suite of optogenetic tools to anatomically isolate Mthal circuitry. I show that an adeno-associated virus injected in upstream structures can be reliably trafficked to and expressed in Mthal. These techniques establish methods to test hypotheses concerning complex spike-LFP and LFP-LFP interactions ultimately leading to a better understanding of how movement signals are mediated by Mthal.