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LTD-like molecular pathways in developmental synaptic pruning

Abstract

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.

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Figure 1: Experience-dependent pruning shapes the cortical circuit architecture.
Figure 2: Impaired CF synapse elimination and deficient PF LTD in mGluR1 knockout mice.
Figure 3: Developmental CF synapse elimination in the rodent cerebellum.
Figure 4: LTD at climbing fiber synapses depends on mGluR1–PKC signaling.
Figure 5: LTD dysregulation and impaired CF pruning in a mouse model of the human 15q11–13 duplication.

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Acknowledgements

We thank B. Kasthuri and members of the Hansel laboratory for comments. M.K. is supported by a Grant-in-Aid for Scientific Research (25000015) from JSPS, Japan, and the Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) from AMED, Japan. C.H. is supported by the Simons Foundation (SFARI 203507 and 311232) and the National Institutes of Health (NS62771).

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Piochon, C., Kano, M. & Hansel, C. LTD-like molecular pathways in developmental synaptic pruning. Nat Neurosci 19, 1299–1310 (2016). https://doi.org/10.1038/nn.4389

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