Inhibitory control of the motor system by the thalamic reticular nucleus

• Applicants: Privatdozent Dr. Philippe Coulon; Professorin Dr. Ilka Diester
• Subject Area: Cognitive, Systems and Behavioural Neurobiology ; Experimental and Theoretical Network Neuroscience ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 523878561

The ability to respond in movement to environmental challenges is central to animal life and requires the neuronal motor system to convert motor plans into muscle activity. The thalamic contribution to motor control is a comparatively recent but well acknowledged finding. Surprisingly, models of the motor system repeatedly omit the thalamic reticular nucleus (TRN). More recent works have shown that the TRN acts as a vital commutator in sensorimotor signalling: Pathophysiological, functional, behavioural, and anatomical evidence show vital roles in movement disorders, epilepsy, motor planning, reward expectation, attention, and action selection. However, research on the role of the TRN in motor control and e.g. in Parkinson's disease is still scarce. We here aim to find the functional link between the TRN as a centre of inhibitory control, and motor signalling of the cortico-basal ganglia loop. It was shown previously, that inhibitory inputs reach TRN neurons from the globus pallidus but these inputs were primarily discussed in the context of attention and have not yet been characterised electrophysiologically. Thus, it seems timely to clarify whether the TRN can provide the mechanism for state dependent initiation of motor programs, initiates inhibitory control in the thalamocortical-basal ganglia-loop, is able to modulate motor activity in the cortex in a state-dependent manner, and whether it plays a role in the switch between motor planning and execution. We will test our hypotheses using 1) the whole-cell patch clamp technique in combination with two-photon calcium imaging and two-photon optogenetic manipulation of TRN neurons and cortical neurons, 2) calcium imaging and optogenetic manipulation of TRN and cortical neurons in freely moving mice performing a delayed reaching task, and 3) by assessing under which conditions and with which activity patterns inhibitory control is established in the proactive delay in the delayed reaching task. We furthermore aim to elucidate whether mechanisms of inhibitory control include post-inhibitory rebound bursting from TRN neurons. The results will further our understanding of motor control, the role and pathways of inhibition in the motor system, and possibly identify the TRN and its mechanisms as a target for future therapeutic interventions.

• DFG Programme: Research Grants