Reticulospinal Function in Health and Recovery from Lesion

When we move, the brain sends commands to the spinal cord via a number of separate pathways. Neural circuits within the spinal cord then interpret these commands to activate muscles, and generate the required movements. Two very important pathways are called the corticospinal tract (CST) and the reticulospinal tract (RST). In primates such as man, the CST appears to be more important in controlling movement than in lower species, and this has led to considerable research concentrating on it. By contrast, we know much less about the RST. What commands are sent via the RST? How are they ?read out? by the spinal cord? How does this differ from the CST? These are the questions that this project seeks to address.

We will make recordings of the electrical activity of single nerve cells in the cerebral cortex (origin of the CST), reticular formation (origin of the RST), and spinal cord, in monkeys trained to perform a reach and grasp task. Using modern methods, we will be able to characterise in detail how these different centres cooperate to control a voluntary movement.

Whilst this information is important in itself if we are to understand the brain, it is also highly relevant to understanding disease. Conditions such as stroke, or spinal cord injury, can interrupt the pathways linking brain and spinal cord. In the months following such damage, most patients show some recovery. It is likely that surviving pathways reconfigure to take over some of the function which is normally performed by the damaged pathways. In the second part of this project, we will interrupt the CST on one side of the brain in monkeys, and wait for them to recover. We will then repeat the single nerve cell recordings carried out in the healthy animals. In this way, we will be able to determine precisely how the RST connections, and the spinal cord?s response to them, change to allow the animal to recover. Understanding this process in its fine details will give us new insights into functional recovery. The knowledge which we gain may suggest better strategies for rehabilitation, allowing doctors and physiotherapists to work with the brain?s own recovery processes to achieve better outcomes.

A number of descending tracts link the brain with the spinal cord. In primates, most research to date has focussed on the corticospinal tract (CST). This is undoubtedly of great importance, as uniquely in higher primates it makes monosynaptic connections to ventral horn motoneurons. However, the reticulospinal tract (RST) is also likely to play an important part in motor control. In non-primates, it has been shown to initiate locomotion, and stabilise posture. Very little information exists on the role played by the RST in primates.

In this application, we will obtain basic information about the reticulospinal system in awake monkeys trained to perform a reach and grasp task. We will record single units from the ponto-medullary reticular formation, characterising the inputs to these cells from the motor cortex and the periphery using electrical stimulation. In the same animal, we will record from motor cortex, identifying neurones which make cortico-reticular projections. We will record from the intermediate zone of the spinal cord, and characterise cortical, reticular and peripheral inputs to spinal cord interneurones. In all three areas, spontaneous activity during task performance will also be recorded. Finally, by stimulating electrically through the recording electrodes, we will identify the muscles which are activated by the cells near to the recording site. This experiment will provide detailed information about the cortico-reticulo-spinal network in healthy animals.

In the second part of the project, animals will be subjected to a unilateral lesion of the CST. After around 6 months recovery, the same recordings as described above will be made. This will allow us to characterise the changes in the network which occur in response to the lesion, and which underlie the functional recovery which is seen. We will be able to identify the extent to which the RST takes over functions previously controlled mainly by the CST. For example, it is known that CST projections have a bias towards the distal muscles of the limbs, RST towards the proximal muscles. One possible result might be that RST projections reorganise to mediate control over distal muscles in the absence of the CST.

These results will provide direct information about the process of functional recovery, and will be immediately relevant to conditions such as stroke and spinal cord injury. This may provide new insights into potential rehabilitation strategies, which at present often do not have a strong scientific foundation.