LTD-like molecular pathways in developmental synaptic pruning

Deficits in developmental synaptic pruning are frequently observed in autism. Here the authors demonstrate molecular pathways shared by pruning and long-term depression (LTD), a synaptic memory mechanism in adult brains that is dysregulated in autism. Thus, autism-related pruning deficits may result from the inability to weaken or disconnect inefficient synapses. In long-term depression (LTD) at synapses in the adult brain, synaptic strength is reduced in an experience-dependent manner. LTD thus provides a cellular mechanism for information storage in some forms of learning. A similar activity-dependent reduction in synaptic strength also occurs in the developing brain and there provides an essential step in synaptic pruning and the postnatal development of neural circuits. Here we review evidence suggesting that LTD and synaptic pruning share components of their underlying molecular machinery and may thus represent two developmental stages of the same type of synaptic modulation that serve different, but related, functions in neural circuit plasticity. We also assess the relationship between LTD and synaptic pruning in the context of recent findings of LTD dysregulation in several mouse models of autism spectrum disorder (ASD) and discuss whether LTD deficits can indicate impaired pruning processes that are required for proper brain development.