Life and Death of Neurons

 A recent study by Cusack et al. , published in the May issue of Nature Communications sheds light on the mechanisms underlying axon pruning and apoptosis. Axon pruning is an essential mechanism as it allows faulty connections to be severed. It is also part of normal development and has an important role to play as part of learning and memory. Axon pruning, although essential for the well being of our brains, can be a dangerous gamble as the poison released by the neuron to severe its axon could kill the entire cell if released improperly. Apoptosis, a more radical mechanism consisting of the intentional destruction of an entire cell is also sometimes required as it permits the weeding out of broken or incorrectly located neurons that could have a negative impact on the body.

The phenomenon of axon pruning has puzzled neuroscientists curious to understand how a neuron can trigger a self-destruct mechanism onto its axon while preventing it from causing the destruction of the entire cell. Earlier research has found that defective axon pruning could be one of the causes underlying neurodevelopmental disorders such as autism or schizophrenia. A greater understanding of the regulatory mechanisms behind axon pruning could thus greatly benefit research into such disorders. Cusack and colleagues’ recent study proposes to uncover the different pathways involved in the distinct mechanisms of pruning and apoptosis. To this end, the research team used mouse neurons which were placed in microfluidic chambers, a special device allowing them to independently manipulate the environments surrounding the axon and the cell body when the different mechanisms of pruning or apoptosis are triggered. It emerged from this study that although both mechanisms use the same poison (a group of molecules known as Caspases), they actually use it in very different ways. In the case of  apoptosis, the neuron deploys the lethal Caspases using an activator known as Apaf-1 whereas during axon pruning, Apaf-1 is not present, despite also involving the use of Caspases. This is a rather exciting discovery as this second pathway for the activation of Caspases was previously unknown.