Axon pruning: an essential step underlying the developmental plasticity of neuronal connections

Abstract

Regressive events play a key role in modifying neural connectivity in early development. An important regressive event is the pruning of neuronal processes. Pruning is a strategy often used to selectively remove exuberant neuronal branches and connections in the immature nervous system to ensure the proper formation of functional circuitry. In the following review, we discuss our present understanding of the cellular and molecular mechanisms that regulate the pruning of axons during neuronal development as well as in neurological diseases. The evidence suggests that there are several similarities between the mechanisms that are involved in developmental axon pruning and axon elimination in disease. In summary, these findings provide researchers with a unique perspective on how developmental plasticity is achieved and how to develop strategies to treat complex neurological diseases.

Double-dissociation between the mechanism leading to impulsivity and inattention in Attention Deficit Hyperactivity Disorder: A resting-state functional connectivity study

“…Increased aberrant connectivity within the cortico-striatal and VAN might be related to a delayed synaptic pruning that occurs during brain maturation (Low and Cheng 2006). Preliminary reports show that ADHD children are on a different trajectory of brain maturation (Shaw et al 2012) that may also have impacted the functional connectivity within the cortico-striatal and ventral fronto-parietal networks.…”

Guidance Molecules in Axon Pruning and Cell Death

“…Axon pruning and neuronal cell death also occur when the nervous system is injured or degenerates (Coleman 2005;Low and Cheng 2006;Luo and O'Leary 2005;Raff et al 2002). In Wallerian degeneration, which occurs after axons are severed, the distal portion of the axon degrades quickly, whereas the neuron itself can often survive and the proximal portion of the axon eventually regrows.…”

“…Axon pruning and neuronal cell death are thought to be controlled by largely distinct cellular mechanisms (Bredesen et al 2006;Buss et al 2006;Buss and Oppenheim, 2004;Low and Cheng, 2006). Axon pruning enables removal of exuberant or misguided axon branches in the absence of cell death, whereas other appropriate connections of the same neuron are maintained.…”

“…T he development of the nervous system involves progressive and regressive events (Cowan et al 1984;Low and Cheng 2006). Progressive events like neural proliferation, neurite outgrowth, and synapse formation set up a broad pattern of neural connectivity.…”

Introduction. The regenerating brain

“…RGMs are re-expressed at lesion sites in the adult CNS, and the authors speculate whether this serves to prevent excessive sprouting and aberrant rewiring or represents an attempted 'replay' of a developmental mechanism. Low & Cheng (2006) review new mechanistic insights into the widespread pruning of axonal processes that occurs during normal development. They also describe recent insights into the related processes of axonal degeneration in degenerative disease or following injury (Wallerian degeneration) and in particular the insights obtained from the analysis of mutant mice in which Wallerian degeneration is dramatically slowed (Wld s mice).…”