State-Dependent Calcium Signaling in Dendritic Spines of Striatal Medium Spiny Neurons

Carter, Adam G.; Sabatini, Bernardo L.

doi:10.1016/j.neuron.2004.10.013

Cited by 308 publications

(357 citation statements)

References 59 publications

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“…Combined two-photon laser scanning microscopy (2PLSM) and two-photon laser photoactivation (2PLP) of MNI-glutamate was performed as described previously (Carter and Sabatini, 2004;Bloodgood and Sabatini, 2007). Whole-cell recordings were obtained from CA1 hippocampal pyramidal neurons in acute rat brain slices (P16 -P19) prepared as described previously (Bloodgood and Sabatini, 2007) using an intracellular solution containing the following (in mM): 140 KMeSO 4 , 8 NaCl, 1 MgCl 2 , 10 HEPES, 5 MgATP, and 0.4 Na 2 GTP, pH 7.3.…”

Section: Methodsmentioning

confidence: 99%

Natural Oligomers of the Alzheimer Amyloid-β Protein Induce Reversible Synapse Loss by Modulating an NMDA-Type Glutamate Receptor-Dependent Signaling Pathway

Shankar

Bloodgood²,

Townsend³

et al. 2007

J. Neurosci.

1,413

1,193

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Alzheimer's disease (AD) is characterized by decreased synapse density in hippocampus and neocortex, and synapse loss is the strongest anatomical correlate of the degree of clinical impairment. Although considerable evidence supports a causal role for the amyloid-␤ protein (A␤) in AD, a direct link between a specific form of A␤ and synapse loss has not been established. We demonstrate that physiological concentrations of naturally secreted A␤ dimers and trimers, but not monomers, induce progressive loss of hippocampal synapses. Pyramidal neurons in rat organotypic slices had markedly decreased density of dendritic spines and numbers of electrophysiologically active synapses after exposure to picomolar levels of soluble oligomers. Spine loss was reversible and was prevented by A␤-specific antibodies or a small-molecule modulator of A␤ aggregation. Mechanistically, A␤-mediated spine loss required activity of NMDA-type glutamate receptors (NMDARs) and occurred through a pathway involving cofilin and calcineurin. Furthermore, NMDARmediated calcium influx into active spines was reduced by A␤ oligomers. Partial blockade of NMDARs by pharmacological antagonists was sufficient to trigger spine loss. We conclude that soluble, low-n oligomers of human A␤ trigger synapse loss that can be reversed by therapeutic agents. Our approach provides a quantitative cellular model for elucidating the molecular basis of A␤-induced neuronal dysfunction.

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Section: Methodsmentioning

confidence: 99%

Natural Oligomers of the Alzheimer Amyloid-β Protein Induce Reversible Synapse Loss by Modulating an NMDA-Type Glutamate Receptor-Dependent Signaling Pathway

Shankar

Bloodgood²,

Townsend³

et al. 2007

J. Neurosci.

1,413

1,193

View full text Add to dashboard Cite

show abstract

“…These are the development of bright, fast, and high-dynamic-range Ca 2þ -sensitive fluorophores; the development and dissemination of two-photon laser-scanning microscopy; and the development of two-photon released caged neurotransmitters that allow direct stimulation of visualized spines (Tsien 1980;Minta et al 1989;Denk et al 1990;Matsuzaki et al 2001;Carter and Sabatini 2004;Yasuda et al 2004). Ca 2þ accumulation within cells and dendritic spines can be visualized through the use of Ca 2þ -sensitive fluorescent molecules that are commonly referred to as "Ca 2þ indicators."…”

Section: Tools To Study Ca 2þ Signaling In Dendritic Spinesmentioning

confidence: 99%

Calcium Signaling in Dendritic Spines

Higley

Sabatini

2012

Cold Spring Harbor Perspectives in Biology

161

167

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“…The analyzed dataset included a variety of genotypes to ascertain how well our algorithm detected spines with a wide distribution of morphologies. In brief, 3D image stacks of neurons were collected using a custom-built two-photon laser scanning microscope [23] with an excitation wavelength of 910 nm. The objective that we use is Olympus LUMPlanFI/RI 60x/0.90 NA, Water immersion.…”

Section: Image Acquisitionmentioning

confidence: 99%

A novel computational approach for automatic dendrite spines detection in two-photon laser scan microscopy

Cheng

Zhou

Miller

et al. 2007

Journal of Neuroscience Methods

Self Cite

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Background-Recent research has shown that there is a strong correlation between the functional properties of a neuron and its morphologic structure. Current morphologic analyses typically involve a significant component of computer-assisted manual labor, which is very time-consuming and is susceptible to operator bias. The existing semi-automatic approaches largely reduce user efforts. However, some manual interventions, such as setting a global threshold for segmentation, are still needed during image processing.Methods-We present an automated approach, which can greatly help neurobiologists obtain quantitative morphological information about a neuron and its spines. The automation includes an adaptive thresholding method, which can yield better segment results than the prevalent global thresholding method. It also introduces an efficient backbone extraction method, a SNR-based, detached spine component detection method, and an attached spine component detection method based on the estimation of local dendrite morphology.Results-The morphology information obtained both manually and automatically are compared in detail. Using the Kolmogov-Smirnov test, we find a 99.13% probability that the dendrite length distributions are the same for the automatic and manual processing methods. The spine detection results are also compared with other existing semi-automatic approaches. The comparison results show that our approach has 33% fewer false positives and 77% fewer false negatives on average.Conclusions-Because the proposed detection algorithm requires less user input and performs better than existing algorithms, our approach can quickly and accurately process neuron images without user intervention.

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State-Dependent Calcium Signaling in Dendritic Spines of Striatal Medium Spiny Neurons

Cited by 308 publications

References 59 publications

Natural Oligomers of the Alzheimer Amyloid-β Protein Induce Reversible Synapse Loss by Modulating an NMDA-Type Glutamate Receptor-Dependent Signaling Pathway

Natural Oligomers of the Alzheimer Amyloid-β Protein Induce Reversible Synapse Loss by Modulating an NMDA-Type Glutamate Receptor-Dependent Signaling Pathway

Calcium Signaling in Dendritic Spines

A novel computational approach for automatic dendrite spines detection in two-photon laser scan microscopy

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