Formation and maturation of synapses in primary cultures of rat cerebral cortical cells: an electron microscopic study

Ichikawa, Masumi; Muramoto, Koji; Kobayashi, Kazuo; Kawahara, Masahiro; Kuroda, Yoichiro

doi:10.1016/0168-0102(93)90076-3

Cited by 138 publications

(115 citation statements)

References 24 publications

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“…Based on nuclear DAPI staining together with double immunostaining with the neuronal marker NeuN and the dendritic marker MAP2, the purity of our neuronal cultures was higher than 95% (data not shown). It is well known that at the end of their first week in vitro primary neuronal cultures enter a maturation period characterized by extensive dendritic branching and synaptogenesis that is most prominent during the second week (Dotti et al, 1988;Ichikawa et al, 1993;Lesuisse and Martin, 2002). Examination of lysates from PS1ϩ/ϩ, PS1ϩ/Ϫ, and PS1Ϫ/Ϫ neurons approaching the end of their second week in culture (13 DIV) revealed that PS1Ϫ/Ϫ neurons are significantly impaired in their ability to activate PI3K/Akt signaling, as indicated by the decreased phosphorylation of both, the PI3K effector protein kinase Akt ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…These maturation activities start at about the end of the first week in vitro and peak at the end of the second week (Dotti et al, 1988;Ichikawa et al, 1993;Lesuisse and Martin, 2002). Neuronal PI3K signaling is activated in response to a variety of stimuli including growth factors (van der Heide et al, 2006), neurotrophins (Mizuno et al, 2003), cell-cell adhesion molecules (Ditlevsen et al, 2003;Loers et al, 2005), and synaptic activity (Perkinton et al, 2002;Sutton and Chandler, 2002;Man et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

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Wild-Type But Not FAD Mutant Presenilin-1 Prevents Neuronal Degeneration by Promoting Phosphatidylinositol 3-Kinase Neuroprotective Signaling

Baki

Neve²,

Shao³

et al. 2008

J. Neurosci.

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The role of presenilin-1 (PS1) in neuronal phosphatidylinositol 3-kinase (PI3K)/Akt signaling was investigated in primary neuronal cultures from wild-type (WT) and PS1 null (PS1؊/؊) embryonic mouse brains. Here we show that in PS1Ϫ/Ϫ cultures, the onset of neuronal maturation coincides with a decrease in the PI3K-dependent phosphorylation-activation of Akt and phosphorylationinactivation of glycogen synthase kinase-3 (GSK-3). Mature PS1Ϫ/Ϫ neurons show increased activation of apoptotic caspase-3 and progressive degeneration preceded by dendritic retraction. Expression of exogenous WT PS1 or constitutively active Akt in PS1Ϫ/Ϫ neurons stimulates PI3K signaling and suppresses both caspase-3 activity and dendrite retraction. The survival effects of PS1 are sensitive to inhibitors of PI3K kinase but insensitive to ␥-secretase inhibitors. Familial Alzheimer disease (FAD) mutations suppress the ability of PS1 to promote PI3K/AKT signaling, prevent phosphorylation/inactivation of GSK-3 and promote activation of caspase-3. These mutation effects are reversed upon coexpression of constitutively active Akt. Together, our data indicate that the neuroprotective role of PS1 depends on its ability to activate the PI3K/Akt signaling pathway and that PS1 FAD mutations increase GSK-3 activity and promote neuronal apoptosis by inhibiting the function of PS1 in this pathway. These observations suggest that stimulation of PI3K/Akt signaling may be beneficial to FAD patients.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Wild-Type But Not FAD Mutant Presenilin-1 Prevents Neuronal Degeneration by Promoting Phosphatidylinositol 3-Kinase Neuroprotective Signaling

Baki

Neve²,

Shao³

et al. 2008

J. Neurosci.

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“…Under the assumption that a culture forms synapses in a monolayer of about 10 µm (thickness of an average cell), the number of synapses per neuron can be up to 800. Ichikawa et al (1993) showed that this number can be as high as 1100 (synapses per neuron). We used a connectivity range (K max ) up to 1100.…”

Section: Network Parametersmentioning

confidence: 99%

“…Neurons in cortical networks receive several thousands of synaptic inputs in vivo and about one thousand in vitro (Van Huizen et al 1985;Ichikawa et al 1993), delays may exceed the 40-ms range in vivo (Swadlow and Waxman 1975) or 20-ms in vitro (Muller et al 1997). Moreover, several experimental studies on synaptogenesis in cortical neuronal cultures show that network activity is correlated with the average number of synapses per neuron (further referred to as connectivity; Habets et al 1987;Muramoto et al 1993).…”

Section: Introductionmentioning

confidence: 99%

Network bursts in cortical cultures are best simulated using pacemaker neurons and adaptive synapses

et al. 2010

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One of the most specific and exhibited features in the electrical activity of dissociated cultured neural networks (NNs) is the phenomenon of synchronized bursts, whose profiles vary widely in shape, width and firing rate. On the way to understanding the organization and behavior of biological NNs, we reproduced those features with random connectivity network models with 5,000 neurons. While the common approach to induce bursting behavior in neuronal network models is noise injection, there is experimental evidence suggesting the existence of pacemaker-like neurons. In our simulations noise did evoke bursts, but with an unrealistically gentle rising slope. We show that a small subset of 'pacemaker' neurons can trigger bursts with a more realistic profile. We found that adding pacemaker-like neurons as well as adaptive synapses yield burst features (shape, width, and height of the main phase) in the same ranges as obtained experimentally. Finally, we demonstrate how changes in network connectivity, transmission delays, and excitatory fraction influence network burst features quantitatively.

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“…By 14 DIV, cortical cultures reach a peak in synaptic density and neuronal cell connectivity (31), which reflects maturation of the neuronal network, paralleled by maturation of electrophysiological properties (32,33). We used the Y188 rabbit monoclonal antibody, which is highly specific for APP (34), and antiNav1.6 antibodies to stain 14 DIV cortical neuron cultures from WT mice and APP KO mice.…”

Section: App Is Colocalized With Nav16 In Mouse Cortical Neurons-mentioning

confidence: 99%

Amyloid Precursor Protein Enhances Nav1.6 Sodium Channel Cell Surface Expression

Liu

Tan

Xiao

et al. 2015

Journal of Biological Chemistry

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Background: Loss-of-function amyloid precursor protein (APP) and Nav1.6 transgenic mice share similar phenotypes. Results: APP interacts with Nav1.6 and enhances its cell surface expression through a G o -coupled JNK pathway. Conclusion: APP regulates Nav1.6 function, likely through a G o -coupled JNK pathway. Significance: This finding advances the current understanding of APP functions and has implications for novel therapies for neurodegenerative disorders.

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Formation and maturation of synapses in primary cultures of rat cerebral cortical cells: an electron microscopic study

Cited by 138 publications

References 24 publications

Wild-Type But Not FAD Mutant Presenilin-1 Prevents Neuronal Degeneration by Promoting Phosphatidylinositol 3-Kinase Neuroprotective Signaling

Wild-Type But Not FAD Mutant Presenilin-1 Prevents Neuronal Degeneration by Promoting Phosphatidylinositol 3-Kinase Neuroprotective Signaling

Network bursts in cortical cultures are best simulated using pacemaker neurons and adaptive synapses

Amyloid Precursor Protein Enhances Nav1.6 Sodium Channel Cell Surface Expression

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