Thalamic control of motor behaviour

Abstract

The primary motor cortex (M1) is a key brain area for the generation and control of motor behaviour. Output from M1 can be driven in part by long-range inputs from a collection of thalamic nuclei termed the motor thalamus (MTh), but how MTh input shapes activity in M1 and forelimb motor behaviour remains largely unresolved. To address this issue, we first defined the 3D anatomical coordinates of mouse forelimb motor thalamus (MThFL) by employing conventional retrograde and virus-based tracing methods targeted to the forelimb region of M1 (M1FL). These complimentary approaches defined MThFL as a ~0.8 mm wide cluster of neurons with anatomical coordinates 1.1 mm caudal, 0.9 mm lateral to bregma and 3.2 mm below the pial surface. Thus, MThFL incorporates defined areas of the ventrolateral, ventral anterior and anteromedial thalamic nuclei.

To investigate the importance of M1FL and MThFL during skilled motor behaviour, we developed and optimised a quantitative behavioural paradigm in which head-restrained mice execute forelimb lever pushes in response to an auditory cue to receive a water reward. Forelimb movement trajectories were mapped using high-speed digital imaging and multi-point kinematic analysis. We inactivated both M1FL and MThFL of mice performing this motor behaviour using a pharmacological strategy, which in both cases resulted in a significant reduction in task performance. Inactivating M1FL significantly affected forelimb coordination and dexterity, resulting in erratic motion and posture. In contrast, mice with MThFL inactivated displayed a reduction in total motor output, although correct posture was maintained. We performed extracellular recordings in MThFL of expert-level mice, demonstrating that motor thalamic output during execution of task was dominated by a robust response to the onset of the auditory cue. Cue-evoked responses were also observed in motor thalamic neurons of naive mice.

We have developed a novel solution to the stability problem encountered when performing whole-cell patch-clamp recordings from the motor cortex of head-restrained mice performing forelimb motor behaviour, and present preliminary recordings maintained through the execution of forelimb behaviour.