Neural circuit rewiring: insights from DD synapse remodeling

Kurup, N S; Jin, Yishi

doi:10.1080/21624054.2015.1129486

Cited by 27 publications

(19 citation statements)

References 36 publications

(63 reference statements)

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“…An ongoing effort to produce a gene expression fingerprint of each type of C. elegans neuron (Hammarlund et al, 2018; Taylor, 2019) may be useful for identifying genetic programs that uniquely correlate with spine morphogenesis since only a small number (White et al, 1976) of neurons have been reported to have spine-like structures. Finally, a developmentally regulated remodeling program (Kurup and Jin, 2016; Petersen et al, 2011; White et al, 1978) transforms presynaptic boutons into postsynaptic spines in larval DD neurons and thus could be especially useful for live imaging studies of synaptic plasticity and spine morphogenesis.…”

Section: Resultsmentioning

confidence: 99%

C. elegans neurons have functional dendritic spines

Cuentas-Condori

Mulcahy

et al. 2019

eLife

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Dendritic spines are specialized postsynaptic structures that transduce presynaptic signals, are regulated by neural activity and correlated with learning and memory. Most studies of spine function have focused on the mammalian nervous system. However, spine-like protrusions have been reported in C. elegans (Philbrook et al., 2018), suggesting that the experimental advantages of smaller model organisms could be exploited to study the biology of dendritic spines. Here, we used super-resolution microscopy, electron microscopy, live-cell imaging and genetics to show that C. elegans motor neurons have functional dendritic spines that: (1) are structurally defined by a dynamic actin cytoskeleton; (2) appose presynaptic dense projections; (3) localize ER and ribosomes; (4) display calcium transients triggered by presynaptic activity and propagated by internal Ca++ stores; (5) respond to activity-dependent signals that regulate spine density. These studies provide a solid foundation for a new experimental paradigm that exploits the power of C. elegans genetics and live-cell imaging for fundamental studies of dendritic spine morphogenesis and function.

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Section: Resultsmentioning

confidence: 99%

C. elegans neurons have functional dendritic spines

Cuentas-Condori

Mulcahy

et al. 2019

eLife

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“…Identification of IF Genes That Regulate Synapse Rewiring. At the end of larval stage 1 (L1), the dorsal D (DD)-type motor neurons rewire their presynaptic connections from the ventral nerve cord (VNC) to the dorsal nerve cord (DNC), concurrent with the birth of ventral D (VD)-type motor neurons, which then form synapses along the VNC (19). We visualized DD-neuron presynaptic terminals using a GFP-tagged synaptobrevin (SNB-1::GFP) reporter (juIs137: P flp-13 SNB-1::GFP).…”

Section: Resultsmentioning

confidence: 99%

Intermediate filament accumulation can stabilize microtubules inCaenorhabditis elegansmotor neurons

Kurup

Goncharov

et al. 2018

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

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Neural circuits utilize a coordinated cellular machinery to form and eliminate synaptic connections, with the neuronal cytoskeleton playing a prominent role. During larval development of , synapses of motor neurons are stereotypically rewired through a process facilitated by dynamic microtubules (MTs). Through a genetic suppressor screen on mutant animals that fail to rewire synapses, and in combination with live imaging and ultrastructural studies, we find that intermediate filaments (IFs) stabilize MTs to prevent synapse rewiring. Genetic ablation of IFs or pharmacological disruption of IF networks restores MT growth and rescues synapse rewiring defects in the mutant animals, indicating that IF accumulation directly alters MT stability. Our work sheds light on the impact of IFs on MT dynamics and axonal transport, which is relevant to the mechanistic understanding of several human motor neuron diseases characterized by IF accumulation in axonal swellings.

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“…Thus, DD rewiring is integral to maturation of the motor circuit. This dramatic synaptic rewiring offers a powerful model in which we can identify genes that are essential for the developmental plasticity of neurons (Kurup and Jin, 2016). …”

Section: Introductionmentioning

confidence: 99%

Myrf ER-Bound Transcription Factors Drive C. elegans Synaptic Plasticity via Cleavage-Dependent Nuclear Translocation

Meng

Tao

et al. 2017

Developmental Cell

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Summary Synaptic refinement is a critical step in nervous system maturation, requiring a carefully timed reorganization and refinement of neuronal connections. We have identified myrf-1, a homologue of Myrf family transcription factors, as a key regulator of synaptic rewiring in C. elegans. MYRF-1 and its paralog MYRF-2 are functionally redundant specifically in synaptic rewiring. They co-exist in the same protein complex, and act cooperatively to regulate synaptic rewiring. We find that the MYRF proteins localize to the endoplasmic reticulum membrane, and that they are cleaved into active N-terminal fragments, which then translocate into the nucleus to drive synaptic rewiring. Over-expression of active forms of MYRF is sufficient to accelerate synaptic rewiring. MYRF-1 and MYRF-2 are the first genes identified to be indispensable for promoting synaptic rewiring in C. elegans. These findings reveal a molecular mechanism underlying synaptic rewiring and developmental circuit plasticity.

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Neural circuit rewiring: insights from DD synapse remodeling

Cited by 27 publications

References 36 publications

C. elegans neurons have functional dendritic spines

C. elegans neurons have functional dendritic spines

Intermediate filament accumulation can stabilize microtubules inCaenorhabditis elegansmotor neurons

Myrf ER-Bound Transcription Factors Drive C. elegans Synaptic Plasticity via Cleavage-Dependent Nuclear Translocation

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