Spontaneous Calcium Transients in Developing Cortical Neurons Regulate Axon Outgrowth

Tang, Fangjun; Dent, Erik W.; Kalil, Katherine

doi:10.1523/jneurosci.23-03-00927.2003

Cited by 120 publications

(115 citation statements)

References 41 publications

(62 reference statements)

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“…Whereas some studies suggest that reducing intracellular levels of calcium can promote growth cone motility and neurite extension (Tang et al 2003), other studies suggest that lowering calcium inhibits these morphological features (Suarez-Isla et al 1984;Mattson and Kater 1987;Cambray-Deakin and Burgoyne 1992), consistent with observations described here. However, even within the same study, both low and high neuronal calcium levels have been shown to induce growth cone collapse (Mattson and Kater 1987;Kater et al 1988), suggesting that growth cone motility, as well as neurite growth and arborization, may require optimal levels of calcium, deviations above or below which result in negative outcomes.…”

Section: Calcium and Neuronal Maturationsupporting

confidence: 89%

Effects of Disrupting Calcium Homeostasis on Neuronal Maturation: Early Inhibition and Later Recovery

et al. 2008

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It has become increasingly clear that agents that disrupt calcium homeostasis may also be toxic to developing neurons. Using isolated primary neurons, we sought to understand the neurotoxicity of agents such as MK801 (which blocks ligand-gated calcium entry), BAPTA (which chelates intracellular calcium), and thapsigargin (TG; which inhibits the endoplasmic reticulum Ca 2+ -ATPase pump). Thus, E18 at cotical neuons wee grown for 1 day in vitro (DIV) and then exposed to vehicle (0.1% DMSO), MK801 (0.01-20 μM), BAPTA (0.1-20 μM), or TG (0.001-1 μM) for 24 h. We found that all three agents could profoundly influence early neuronal maturation (growth cone expansion, neurite length, neurite complexity), with the order of potency being MK801 < BAPTA < TG. We next asked if cultures exposed to these agents were able to re-establish their developmental program once the agent was removed. When we examined network maturity at 4 and 7 DIV, the order of recovery was MK801 > BAPTA > TG. Thus, mechanistically distinct ways of disrupting calcium homeostasis differentially influenced both short-term and long-term neuronal maturation. These observations suggest that agents that act by altering intracellular calcium and are used in obstetrics or neonatology may be quite harmful to the still-developing human brain.

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Section: Calcium and Neuronal Maturationsupporting

confidence: 89%

Effects of Disrupting Calcium Homeostasis on Neuronal Maturation: Early Inhibition and Later Recovery

et al. 2008

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“…Calcium imaging and analysis were performed as previously described (Tang et al, 2003;Tang and Kalil, 2005). Briefly, 18 -72 h after plating cell cultures were loaded with 4 M Fluo4 AM (Invitrogen) for 30 min.…”

Section: Methodsmentioning

confidence: 99%

“…In most cases, calcium activity was measured in the axon or the growth cone and levels of intracellular Ca 2ϩ were found to be inversely correlated with rates of axon outgrowth (Gomez and Spitzer, 1999;Tang et al, 2003;Jacques-Fricke et al, 2006) or changes in the direction of axon growth (Nishiyama et al, 2003;Wen et al, 2004). In previous studies, we found that global Ca 2ϩ transients inhibited extension of the primary axon (Tang et al, 2003), whereas localized Ca 2ϩ transients evoked by netrin-1 signaling could promote branching of the axon in regions of high-frequency Ca 2ϩ transients (Tang and Kalil, 2005). It has been well established that competitive activity-dependent mechanisms can regulate synaptic innervation at target sites.…”

Section: Introductionmentioning

confidence: 99%

Differential Outgrowth of Axons and their Branches Is Regulated by Localized Calcium Transients

Hutchins¹,

Kalil²

2008

J. Neurosci.

110

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During development axon outgrowth and branching are independently regulated such that axons can stall or retract while their interstitial branches extend toward targets. Previous studies have shown that guidance cues and intracellular signaling components can promote branching of cortical axons without affecting axon outgrowth. However, the mechanisms that regulate differential outgrowth of axons and their branches are not well understood. Based on our previous work showing the importance of localized repetitive calcium transients in netrin-1-induced cortical axon branching, we sought to investigate the role of calcium signaling in regulating differential outgrowth of axons and their branches. Using fluorescence calcium imaging of dissociated developing cortical neurons, we show that localized spontaneous calcium transients of different frequencies occur in restricted regions of axons and their branches. Higher frequencies occur in more rapidly extending processes whereas lower frequencies occur in processes that stall or retract. Direct induction of localized calcium transients with photolysis of caged calcium induced rapid outgrowth of axonal processes. Surprisingly outgrowth of one axonal process was almost invariably accompanied by simultaneous retraction of another process belonging to the same axon, suggesting a competitive mechanism for differential process outgrowth. Conversely, reducing frequencies of calcium transients with nifedipine and TTX reduced the incidence of differential process outgrowth. Together these results suggest a novel activity-dependent mechanism whereby intrinsic localized calcium transients regulate the competitive growth of axons and their branches. These mechanisms may also be important for the development of cortical connectivity in vivo.

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“…Dynamic Ca 2+ changes have been reported in the developing cortex (Yuste et al 1992) and these Ca 2+ transients could be responsible for the axonal outgrowth. Th e incidence of Ca 2+ transients highly correlated with axonal growth cone morphologies and behaviors (Tang et al 2003).…”

Section: Th E Role Of Calcium In Neurite Growthmentioning

confidence: 99%

Mechanisms involved in the regulation of neuropeptide-mediated neurite outgrowth: a minireview

Lestanova

Bačová

Bakoš

2016

Endocrine Regulations

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Th e present knowledge, regarding the neuronal growth and neurite extension, includes neuropeptide action in the central nervous system. Research reports have brought much information about the multiple intracellular signaling pathways of neuropeptides. However, regardless of the diff erences in the local responses elicited by neuropeptides, there exist certain functional similarities in the eff ects of neuropeptides, mediated by their receptors. In the present review, data of the relevant studies, focused on G protein-coupled receptors activated by neuropeptides, are summarized. Particularly, receptors that activate phosphatidylinositol-calcium system and protein kinase C pathways, resulting in the reorganization of the neuronal cytoskeleton and changes in the neuronal morphology, are discussed. Based on our data received, we are showing that oxytocin increases the gene expression of GTPase cell division cycle protein 42 (Cdc42), implicated in many aspects of the neuronal growth and morphology. We are also paying a special attention to neurite extension and retraction in the context of neuropeptide regulation.

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Spontaneous Calcium Transients in Developing Cortical Neurons Regulate Axon Outgrowth

Cited by 120 publications

References 41 publications

Effects of Disrupting Calcium Homeostasis on Neuronal Maturation: Early Inhibition and Later Recovery

Effects of Disrupting Calcium Homeostasis on Neuronal Maturation: Early Inhibition and Later Recovery

Differential Outgrowth of Axons and their Branches Is Regulated by Localized Calcium Transients

Mechanisms involved in the regulation of neuropeptide-mediated neurite outgrowth: a minireview

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