Tuning spinal motoneurons for movement. (360G-Wellcome-110193_Z_15_Z)

My overall aim is to understand how neural circuits are organised in order to control motor behaviour. Furthermore, I aim to understand dysfunction of these circuits in disease or injury in order to form the foundation for strategies to improve motor function. My research programme includes neural circuit studies in mice and in humans. Here, I will focus on one key question: how are spinal motoneurons tuned in order to produce trains of action potentials of appropriate frequencies so as to achieve the muscle contraction required for a particular motor task? This application is based on the hypothesis that motoneurons learn these firing frequencies during development, and adjust their expression of potassium channels located at sites post-synaptic to C-boutons, large cholinergic terminals forming neuromodulatory synapses on motoneuronal somata. We will address three specific aims: Aim 1: to characterise the development of SK channels, motoneuron excitability, and C-boutons Aim 2: to determine the role of Kv2.1 channels in motoneuron excitability and and C-bouton physiology Aim 3: to establish whether homeostatic mechanisms determine motoneuron.