Completed Brain & Nervous System Psychology & Behaviour

Tuning spinal motoneurons for movement.

Funder Wellcome Charity-funded
Recipient organisation University College London
Funding £2.5M
Period Apr 2016 — Apr 2021

In plain English

AI plain-English summary

Every time you move a muscle, a spinal motoneuron fires a carefully calibrated burst of electrical impulses to make it contract with just the right force. The problem is that no one knows how these motoneurons learn to fire at the correct frequency for a given task. This research tests the idea that motoneurons tune themselves during development by adjusting potassium channels at specific sites called C-boutons—large cholinergic synapses that sit directly on the motoneuron’s cell body and modulate its excitability. If the hypothesis holds, it would reveal a fundamental mechanism by which the nervous system calibrates motor output. That knowledge could eventually inform strategies to restore movement after spinal cord injury or in motor neuron disease, where this tuning goes wrong. But this is primarily fundamental science: the immediate goal is to understand how a healthy spinal circuit works, not to build a therapy. Past discoveries about how neurons regulate their firing have underpinned everything from pacemakers to deep-brain stimulation, so a deeper grasp of motoneuron tuning may open unexpected routes to repairing movement.

View original technical description
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.

View the original record at the funder ↗

Researchers

Robert Brownstone (EPMC Awardee)

Related Research

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Original classification

Investigator Award in Science

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