Dendritic Spines and Development: Towards a Unifying Model of Spinogenesis—A Present Day Review of Cajal's Histological Slides and Drawings

García-López, Pablo; García-Marín, Virginia; Freire, Miguel

doi:10.1155/2010/769207

Cited by 32 publications

(33 citation statements)

References 115 publications

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“…5E), and the spine population did not exhibit an increase in spine length (Fig. 5G), which would have been expected after induction of filopodia, which have been reported to be much longer than spines (3–40 μ m compared to 0.2–2μm; (Garcia-Lopez et al, 2010)).…”

Section: Resultsmentioning

confidence: 51%

Aβ-mediated spine changes in the hippocampus are microtubule-dependent and can be reversed by a subnanomolar concentration of the microtubule-stabilizing agent epothilone D

et al. 2016

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Dendritic spines represent the major postsynaptic input of excitatory synapses. Loss of spines and changes in their morphology correlate with cognitive impairment in Alzheimer’s disease (AD) and are thought to occur early during pathology. Therapeutic intervention at a preclinical stage of AD to modify spine changes might thus be warranted. To follow the development and to potentially interfere with spine changes over time, we established a long term ex vivo model from organotypic cultures of the hippocampus from APP transgenic and control mice. The cultures exhibit spine loss in principal hippocampal neurons, which closely resembles the changes occurring in vivo, and spine morphology progressively changes from mushroom-shaped to stubby. We demonstrate that spine changes are completely reversed within few days after blocking amyloid-β (Aβ) production with the gamma-secretase inhibitor DAPT. We show that the microtubule disrupting drug nocodazole leads to spine loss similar to Aβ expressing cultures and suppresses DAPT-mediated spine recovery in slices from APP transgenic mice. Finally, we report that epothilone D (EpoD) at a subnanomolar concentration, which slightly stabilizes microtubules in model neurons, completely reverses Aβ-induced spine loss and increases thin spine density. Taken together the data indicate that Aβ causes spine changes by microtubule destabilization and that spine recovery requires microtubule polymerization. Moreover, our results suggest that a low, subtoxic concentration of EpoD is sufficient to reduce spine loss during the preclinical stage of AD.

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Section: Resultsmentioning

confidence: 51%

Aβ-mediated spine changes in the hippocampus are microtubule-dependent and can be reversed by a subnanomolar concentration of the microtubule-stabilizing agent epothilone D

et al. 2016

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“…For example, pyramidal cell spine density in human DLPFC increases rapidly after birth and peaks in childhood, at which point spine density begins to decline until stabilizing in the third decade of life (Petanjek et al, 2011). Spine morphology also changes across development, transitioning from filopodia-shaped thin spines early in development to larger spines with a defined head and neck (commonly referred to as mushroom spines) (Garcia-Lopez et al, 2010), one hallmark of a stable axospinous synapse. Cortical axospinous synapses which survive pruning are generally less dynamic than those present earlier in development, becoming relatively stable in both shape and density (Lin and Koleske, 2010).…”

Section: Developmental Trajectory Of Cortical Spine Densitymentioning

confidence: 99%

Dendritic spine pathology in schizophrenia

2013

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Schizophrenia is a neurodevelopmental disorder whose clinical features include impairments in perception, cognition and motivation. These impairments reflect alterations in neuronal circuitry within and across multiple brain regions that are due, at least in part, to deficits in dendritic spines, the site of most excitatory synaptic connections. Dendritic spine alterations have been identified in multiple brain regions in schizophrenia, but are best characterized in layer 3 of the neocortex, where pyramidal cell spine density is lower. These spine deficits appear to arise during development, and thus are likely the result of disturbances in the molecular mechanisms that underlie spine formation, pruning, and/or maintenance. Each of these mechanisms may provide insight into novel therapeutic targets for preventing or repairing the alterations in neural circuitry that mediate the debilitating symptoms of schizophrenia.

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“…Several different models exist for the establishment of synaptic connections, but these do not take into account correlations in the degree distribution (Yoshihara et al 2009; García-López et al 2010). We studied whether correlations in the degree distribution could emerge from associative plasticity.…”

Section: Resultsmentioning

confidence: 99%

Anti-correlations in the degree distribution increase stimulus detection performance in noisy spiking neural networks

2016

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Neuronal circuits in the rodent barrel cortex are characterized by stable low firing rates. However, recent experiments show that short spike trains elicited by electrical stimulation in single neurons can induce behavioral responses. Hence, the underlying neural networks provide stability against internal fluctuations in the firing rate, while simultaneously making the circuits sensitive to small external perturbations. Here we studied whether stability and sensitivity are affected by the connectivity structure in recurrently connected spiking networks. We found that anti-correlation between the number of afferent (in-degree) and efferent (out-degree) synaptic connections of neurons increases stability against pathological bursting, relative to networks where the degrees were either positively correlated or uncorrelated. In the stable network state, stimulation of a few cells could lead to a detectable change in the firing rate. To quantify the ability of networks to detect the stimulation, we used a receiver operating characteristic (ROC) analysis. For a given level of background noise, networks with anti-correlated degrees displayed the lowest false positive rates, and consequently had the highest stimulus detection performance. We propose that anti-correlation in the degree distribution may be a computational strategy employed by sensory cortices to increase the detectability of external stimuli. We show that networks with anti-correlated degrees can in principle be formed by applying learning rules comprised of a combination of spike-timing dependent plasticity, homeostatic plasticity and pruning to networks with uncorrelated degrees. To test our prediction we suggest a novel experimental method to estimate correlations in the degree distribution.Electronic supplementary materialThe online version of this article (doi:10.1007/s10827-016-0629-1) contains supplementary material, which is available to authorized users.

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Dendritic Spines and Development: Towards a Unifying Model of Spinogenesis—A Present Day Review of Cajal's Histological Slides and Drawings

Cited by 32 publications

References 115 publications

Aβ-mediated spine changes in the hippocampus are microtubule-dependent and can be reversed by a subnanomolar concentration of the microtubule-stabilizing agent epothilone D

Aβ-mediated spine changes in the hippocampus are microtubule-dependent and can be reversed by a subnanomolar concentration of the microtubule-stabilizing agent epothilone D

Dendritic spine pathology in schizophrenia

Anti-correlations in the degree distribution increase stimulus detection performance in noisy spiking neural networks

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