What role do motor neurons play in basic bodily functions?

As you read this, muscles are contracting and relaxing regularly to move air in and out of your lungs. When you walk to the kitchen for a cup of coffee, muscles in your legs contract and relax in rhythmic sequence to move you forward. For animals to function, motor behaviours like breathing and walking must be reliably controlled by the nervous system. Muscles need to contract in the same order, for roughly the same duration, each time a breath or step is taken. There is a pattern of activity that must be maintained. But the system also has to be flexible enough to respond to changes in the environment, such as obstacles in your path that you have to step around. There are many open questions about how the nervous system controls rhythmic movements, permitting reliability and flexibility. What determines the timing of the motor pattern? Under what conditions can the timing be altered, and how? To what extent can these behaviours be recovered after injury?

How does the nervous system produce the rhythmic sequence of movements required for walking?
Image credit: Eadward Muybridge 1887, via Boston Public Library

Rhythmic motor pattern generation

Example of a motor network, in which motor neurons are not part of the CPG. Image credit: E. McKiernan.

Rhythmic motor behaviours are controlled by networks of neurons which communicate electrically and chemically¹. Although the exact organization of these networks varies, many can be divided into four principal groups of cells. One group includes a subset of neurons in the central nervous system called a central pattern generating (CPG) network, which produces the core rhythm. In some systems, motor neurons, which send signals directly to muscle fibres, participate in generating the rhythm and are part of the first group. However, in other systems, motor neurons do not belong to the CPG network and are considered a second group receiving input from the first. Muscle fibres constitute a third group of cells comprising whole muscles that contract or relax to produce movements. A fourth group, sensory neurons, responds to the movement of muscles and sends feedback to the central nervous system about the output that was produced, or whether there are environmental perturbations, like obstacles.

Investigating Fragile X syndrome

Our research focuses on the neurons in networks in the brain and aims to understand the mechanisms that underlie the workings of our minds.

Our approach is to study how networks of nerve cells in the brain communicate together, how they connect with each other and how a change in a single gene in the brain can alter a brain network. The Human Genome Project has shown that humans have 20-25,000 different genes. We're still working on the exact number, but current estimates put it at 23,229¹. Around 20,000 (86%) of these genes are thought to express in our brains², but again, the exact count is unknown. Given these vast numbers, it may seem surprising that one gene can have a strong effect. But a single gene really can cause the difference between say a normal IQ and having learning difficulties & cognitive impairments. For example, take the intellectual disability and autism disorder, Fragile X syndrome: people with this monogenic disorder have an impairment of one specific gene³. This results in cognitive impairments, anxiety, higher levels of autism & epilepsy along with other non-cognitive symptoms. Within the brain itself, we find the structural connections made between nerve cells, the synapses, look different to those in an unaffected brain. The synapses are more immature in their development, on average, and are more abundant in the brain.

Synapses in a typical brain network, and those in a Fragile X network.
Image credit: Meredith lab, VU University Amsterdam

But how do we study the effects of a single gene on brain cell networks in a cognitive disorder? And is the increased number of structural connections between nerve cells in Fragile X syndrome reflected in brain function? To directly test our ideas that there are changes occurring in brain networks due to a single gene, we use brain tissue from  genetically-engineered mice to measure functional connections between nerve cells. We test if a nerve cell is connected to its immediate neighbours ('short-range') or to more distant nerve cells ('long-range' partners) using a combination of electrodes to measure neural activity and fluorescent dyes that monitor changes in brain network activity⁴.