Thalamic control of motor cortex activity during skilled motor behaviour

• Applicant: Professorin Dr. Julia Schiemann
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: from 2015 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 277905506

Being able to perform accurate, goal-oriented movements is of fundamental importance to our everyday lives. But how do different brain areas act in concert to generate complex, coordinated motor movements? The primary motor cortex (M1) and motor thalamus play key roles in planning, initiation and execution of complex movements. The subcortical location of the motor thalamus means that it is perfectly positioned to act as a 'transfer hub' routing sensorimotor information from subcortical structures, such as the basal ganglia - which integrate motivational contexts for the selection of motor programmes - and cortical structures directly engaged in generating muscle movement. Previous work has greatly advanced our understanding of how firing patterns of motor cortical and thalamic neurons relate to motor behaviour. However, we still know little about the subthreshold cellular mechanisms that transform motor thalamic input to behaviourally-relevant spike output patterns in M1. To what extent does ongoing thalamic input drive M1 neuronal output? Moreover, the role of basal ganglia-motor thalamus circuits for controlling the activity of neurons in the output layer of M1 (layer 5B) and for initiating goal-oriented, voluntary movements remains largely unexplored. Understanding how information is processed and propagated along the basal ganglia-thalamocortical pathway is of fundamental importance if we are to truly understand the mechanistic basis of diseases that affect this pathway, such as Parkinson's disease. During my fellowship I aim to investigate how motor thalamic input 'shapes' the sub- and suprathreshold activity of layer 5B output neurons in mouse M1 during skilled forelimb movements. To achieve this aim, I will employ a multilevel strategy combining state-of-the-art in vivo whole-cell patch-clamp electrophysiology and 2-photon calcium imaging in awake mice; behavioural motor task training; virus-based neural circuit mapping and chemogenetic inactivation strategies. This combination of top-down (quantitative behaviour) and bottom-up (single cell electrophysiology and imaging) approaches will yield important new insights into how single pyramidal-tract neurons in M1 encode thalamocortical information from the basal ganglia during skilled motor movements.

• DFG Programme: Research Fellowships
• International Connection: United Kingdom
• Host: Professor Dr. Ian Duguid