Deleting Neurons: A closer look at Synaptic Pruning

Abstract

The overproduction of neural elements, including neurons, axons, and synapses, is a tool commonly used in developmental neuroscience to reconstruct nervous systems. This generation and maturation of these neuronal synapses are accompanied by a so-called "pruning" process, marking a peak in synapse elimination (synaptic pruning) which is a final stage in the development of the human brain. Analogous to cleaning up of the brain, synaptic pruning eliminates extra neurons and synaptic connections to increase the efficiency of neuronal transmissions along with eliminating weaker synaptic contacts while stronger connections are kept and strengthened. Brain plasticity is a result of this neural "pruning"; neurons that are more frequently activated are preserved, while those forming weaker synaptic contacts are "trimmed away." Research in zebrafish and rat models have shown pruning occurring in about 80 per cent of the synapses, barring the largest ones. These larger synapses were found to be associated with the most stable and crucial memories residing in the brain. Recent studies indicate that glial cells(microglia and astrocytes) play a critical role in synaptic pruning, mediated by a set of signalling pathways between neurons and glia, identifying and removing unnecessary neural connections. This loss of redundant pathways may explain the arduous task of recovering from a traumatic brain injury; eliminating synaptic redundancies diminishes our ability to develop alternative pathways to bypass the damaged regions. Brain imaging and postmortem anatomical studies have pointed to insufficient or excessive synaptic pruning that may underlie several neurodevelopmental disorders, including autism, schizophrenia, and epilepsy. In this review, we explore the brains innate delete button and present current data on the mechanisms of glial-cell-dependent synaptic pruning by outlining their potential contribution to neurodevelopmental disorders.