Reversing the Outcome of Synapse Elimination at Developing Neuromuscular Junctions In Vivo: Evidence for Synaptic Competition and Its Mechanism

Turney, Stephen G.; Lichtman, Jeff W.

doi:10.1371/journal.pbio.1001352

Cited by 72 publications

(81 citation statements)

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“…In human and nonhuman primate brains, axonal growth during development is correlated with increased FA values in the association fibers (53,54). Neural activity has been shown to result in the growth and branching of axonal fibers (55)(56)(57)(58)(59)(60). This type of activity-dependent axonal growth may have occurred in subjects during immersion, which may contribute to higher FA values.…”

Section: Discussionmentioning

confidence: 99%

Brain white matter structure and COMT gene are linked to second-language learning in adults

Mamiya

Richards

Coe

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Adult human brains retain the capacity to undergo tissue reorganization during second-language learning. Brain-imaging studies show a relationship between neuroanatomical properties and learning for adults exposed to a second language. However, the role of genetic factors in this relationship has not been investigated. The goal of the current study was twofold: (i) to characterize the relationship between brain white matter fiber-tract properties and second-language immersion using diffusion tensor imaging, and (ii) to determine whether polymorphisms in the catechol-O-methyltransferase (COMT) gene affect the relationship. We recruited incoming Chinese students enrolled in the University of Washington and scanned their brains one time. We measured the diffusion properties of the white matter fiber tracts and correlated them with the number of days each student had been in the immersion program at the time of the brain scan. We found that higher numbers of days in the English immersion program correlated with higher fractional anisotropy and lower radial diffusivity in the right superior longitudinal fasciculus. We show that fractional anisotropy declined once the subjects finished the immersion program. The relationship between brain white matter fiber-tract properties and immersion varied in subjects with different COMT genotypes. Subjects with the Methionine (Met)/Valine (Val) and Val/Val genotypes showed higher fractional anisotropy and lower radial diffusivity during immersion, which reversed immediately after immersion ended, whereas those with the Met/Met genotype did not show these relationships. Statistical modeling revealed that subjects' grades in the language immersion program were best predicted by fractional anisotropy and COMT genotype.genetic variation | short-term plasticity | dopamine S econd-language learning in adulthood is becoming increasingly prevalent as globalization advances. Previous studies show that gray matter volume and density are related to foreign language speech learning (1, 2), and that the degree of volumetric change in an individual predicts the level of foreign language proficiency achieved by that person (3, 4). Recent studies using diffusion tensor imaging (DTI) techniques further show that diffusion properties of brain white matter structure are correlated with foreign language learning (5-7). One of these studies demonstrated that the changes in diffusion properties predicted students' second-language proficiency at the end of a language immersion program (7). These findings suggest that the properties of brain structure change with the acquisition of a new language, and that the adult human brain is capable of tissue reorganization in response to intense use of a new language after the putative "critical period."What remains unknown is whether and how genetic factors are related to brain white matter fiber-tract properties as learning ensues. Cumulative evidence using DTI analysis has suggested that brain white matter fiber-tract properties are related to skill learning ...

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Section: Discussionmentioning

confidence: 99%

Brain white matter structure and COMT gene are linked to second-language learning in adults

Mamiya

Richards

Coe

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…These aneural AChR-rich islands likely result from pruning of presynaptic terminal branches, as demonstrated by the vital imaging findings presented below. Recent studies strongly argue that such branch pruning occurs at developing NMJs and drives synapse elimination (11,16).…”

Section: Increased Axo-glial Nrg1-iii Signaling Induces Profound Morpmentioning

confidence: 99%

“…This elimination involves the remodeling of terminal arbors and withdrawal of displaced branches rather than motor neuron death. Vital imaging of developing NMJs has provided compelling evidence that competition among axons determines the sole winner (11,12). Activity patterns (13,14) and the relative efficacy of converging presynaptic inputs (15) are factors known to influence the rate of elimination and the winner.…”

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Neuregulin1 displayed on motor axons regulates terminal Schwann cell-mediated synapse elimination at developing neuromuscular junctions

Lee

Li²,

Mikesh

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Synaptic connections in the nervous system are rearranged during development and in adulthood as a feature of growth, plasticity, aging, and disease. Glia are implicated as active participants in these changes. Here we investigated a signal that controls the participation of peripheral glia, the terminal Schwann cells (SCs), at the neuromuscular junction (NMJ) in mice. Transgenic manipulation of the levels of membrane-tethered neuregulin1 (NRG1-III), a potent activator of SCs normally presented on motor axons, alters the rate of loss of motor inputs at NMJs during developmental synapse elimination. In addition, NMJs of adult transgenic mice that expressed excess axonal NRG1-III exhibited continued remodeling, in contrast to the more stable morphologies of controls. In fact, synaptic SCs of these adult mice with NRG1-III overexpression exhibited behaviors evident in wild type neonates during synapse elimination, including an affinity for the postsynaptic myofiber surface and phagocytosis of nerve terminals. Given that levels of NRG1-III expression normally peak during the period of synapse elimination, our findings identify axon-tethered NRG1 as a molecular determinant for SC-driven neuromuscular synaptic plasticity.synapse elimination | neuromuscular junction | Schwann cell | neuregulin1 | synaptic competition S ynaptic connections found in the mature nervous system differ significantly from those formed during development. This developmental transformation includes elimination and remodeling of existing synapses, commonly termed "synapse elimination," and is seen throughout the nervous system (1, 2). Similar remodeling can occur throughout life during learning, aging, and disease, however (3-5).The process of synapse elimination has been studied most extensively in rodent neuromuscular junctions (NMJs). At each mature NMJ, high-density aggregates of acetylcholine receptors (AChRs) on the muscle fiber are apposed precisely by the terminal arbor of a motor axon. Processes of nonmyelinating gliaterminal Schwann cells (tSCs)-cap this synaptic structure. These tSCs sense the release of acetylcholine and ATP by the nerve and in turn influence transmitter release (6, 7). During 2-3 wk of postnatal development, pruning of up to ∼10 converging motor axons occurs until one axon remains at each NMJ (8-10). This elimination involves the remodeling of terminal arbors and withdrawal of displaced branches rather than motor neuron death. Vital imaging of developing NMJs has provided compelling evidence that competition among axons determines the sole winner (11,12). Activity patterns (13,14) and the relative efficacy of converging presynaptic inputs (15) are factors known to influence the rate of elimination and the winner. Nevertheless, despite these findings, the cellular mechanisms or molecules that govern this process remain largely unknown.We recently observed novel tSC behaviors at neonatal junctions, with tSCs phagocytosing nerve terminals and competing with them for contact with the muscle surface (16). These activitie...

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“…One is eliminated because the other is retained; this is a sort of "zero-sum" game. Synapse selection has been implicated in the formation of abnormal ocular dominance columns in mammals, as well as the formation of the neuromuscular junction (see Wong and Lichtman 2002;Turney and Lichtman 2012).…”

Section: A Generalized Se Theory Of Functionmentioning

confidence: 99%

A Generalized Selected Effects Theory of Function

Garson¹

2017

Philos. of Sci.

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I present and defend the generalized selected effects theory (GSE) of function.According to GSE, the function of a trait consists in the activity that contributed to its bearer's differential reproduction, or differential retention, within a population. Unlike the traditional selected effects (SE) theory, it does not require that the functional trait helped its bearer reproduce; differential retention is enough. Although the core theory has been presented previously, I go significantly beyond those presentations by providing a new argument for GSE and defending it from a recent objection. I also sketch its implications for teleosemantics and philosophy of medicine.

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Reversing the Outcome of Synapse Elimination at Developing Neuromuscular Junctions In Vivo: Evidence for Synaptic Competition and Its Mechanism

Abstract: Competition between neurons for the same synaptic sites at the developing neuromuscular junction drives synaptic rearrangements.

Cited by 72 publications

References 49 publications

Brain white matter structure and COMT gene are linked to second-language learning in adults

Brain white matter structure and COMT gene are linked to second-language learning in adults

Neuregulin1 displayed on motor axons regulates terminal Schwann cell-mediated synapse elimination at developing neuromuscular junctions

A Generalized Selected Effects Theory of Function

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