Motor function is critical to human survival as it governs fundamental behaviours such as locomotion, breathing, speech, feeding and social interaction. Thus, even minor impairment of motor activity can severely hamper quality of life while major impairments, as occur in the neurodegenerative disorder amyotrophic lateral sclerosis (ALS), can be life-threatening. These conditions are characterized by lesions to the spinal cord, a region dedicated to the generation of motor behaviours such as walking and swimming. The spinal cord is composed of central pattern generating circuits, a series of evolutionarily conserved neural networks composed of rhythm-generating interneurons that transmit information directly to the motor neurons that execute muscle contractions. Disruption in the function of interneurons or motor neurons within these circuits can have severe consequences to motor performance and thus survival.
Over the past two decades, due to their unique combination of chemical and physical properties, carbon based nanomaterials have garnered increasing interest as tools for biomedical applications in the field of neuroscience. Among these, graphene possess the simplest structure, being formed by a mono-layer of carbon atoms. Other carbon based nanomaterials derive from it, such as graphene oxide (GO), a functionalized form of graphene containing carbon, oxygen, and hydrogen in variable ratios, and carbon nanotubes, cylindrically-shaped nanostructures composed of graphene sheets that are rolled to form hollow tubes. Recent evidence has showed that these nanomaterials are able to interact with cells of the nervous system and to modulate their function. This holds a great potential for the development of a novel class of nanomaterials based therapeutics for the rescue of defects in the brain. However, the effect of these materials on neuronal network in vivo and on animal behaviour has been poorly understood yet.
To investigate this issue, we have used larval zebrafish as an in vivo model. Early stage zebrafish are ideally suited for this purpose as they are amenable to a broad range of in vivo methodologies, including patch clamp electrophysiology to characterize the electrical activity of neurons, confocal imaging to examine neuronal morphology and behavioural analysis to study their locomotor activity. The purpose of this project was to use zebrafish models to determine whether carbon based nanomaterials could be exploited for the modulation of spinal neuronal activity and of correlated locomotor behaviour in vivo, with the final aim to explore the potential of these materials as novel therapeutics for the cure of nervous system pathologies.
