Redistribution of microtubules in dendrites of hippocampal CA1 neurons after tetanic stimulation during long-term potentiation

Department of Neurosurgery, Fujita Health University, Aichi, Japan.
Italian journal of anatomy and embryology = Archivio italiano di anatomia ed embriologia 01/2008; 113(1):17-27.
Source: PubMed


It is now well accepted that the trafficking of AMPA receptors to the postsynaptic plasma membrane plays an essential role in long-term potentiation at the hippocampal Schaffer collateral synapses on CA1 pyramidal cells, but the motor mechanism of trafficking is unknown. We suspected that this trafficking of AMPA receptors during long-term potentiation may be carried out along microtubules by their motors. To ascertain this hypothesis, we light- and electron-microscopically studied the distribution of microtubules in dendrites of CA1 neurons of non-stimulated and stimulated rat hippocampal slices by using very strong tetanic stimulation for inducing long-term potentiation. As a result, we observed the following changes: 1. In immunofluorescence for microtubules and IP3 receptor using ultrathin-cryosections, linear signals of microtubules in main dendritic shafts were changed into fragmented. 2. Many spotty signals of microtubules emerged at the peripheral area of dendrites. Electron-microscopically, there was redistribution of microtubules in dendritic spines and dendritic shafts, and the thickening of post-synaptic density. 3. Many microtubules concentrated to thickened postsynaptic density in spines and new ones emerged, going to spines from dendritic shafts. These results strongly suggest that new tracks of microtubules from cell bodies to the stimulated postsynaptic membranes were produced after tetanic stimulation during long-term potentiation. This newly produced microtubules between stimulated postsynaptic membranes and the cell body must be the most promising candidate of the track for the trafficking of AMPA receptors to the stimulated postsynaptic plasma membrane.

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    • "Dynamic microtubules in dendritic shafts can transiently enter dendritic spines and dendritic filopodia, the precursors of spines (Gu et al. 2008; Hu et al. 2008; Jaworski et al. 2009; Dent et al. 2011). The frequency of invasion is low, with approximately 1% of dendritic protrusions containing a microtubule at any one time (Hu et al. 2008) and the dwell time is in the order of minutes but, importantly, dwell time and the frequency of invasion are enhanced by synaptic activity (Gu et al. 2008; Hu et al. 2008; Mitsuyama et al. 2008; Jaworski et al. 2009). Microtubules invading spines are oriented with their plus-ends, the end at which tubulin assembly occurs preferentially, distal, i.e., directed toward the spine head. "
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    ABSTRACT: During development, dynamic changes in the axonal growth cone and dendrite are necessary for exploratory movements underlying initial axo-dendritic contact and ultimately the formation of a functional synapse. In the adult central nervous system, an impressive degree of plasticity is retained through morphological and molecular rearrangements in the pre- and post-synaptic compartments that underlie the strengthening or weakening of synaptic pathways. Plasticity is regulated by the interplay of permissive and inhibitory extracellular cues, which signal through receptors at the synapse to regulate the closure of critical periods of developmental plasticity as well as by acute changes in plasticity in response to experience and activity in the adult. The molecular underpinnings of synaptic plasticity are actively studied and it is clear that the cytoskeleton is a key substrate for many cues that affect plasticity. Many of the cues that restrict synaptic plasticity exhibit residual activity in the injured adult CNS and restrict regenerative growth by targeting the cytoskeleton. Here, we review some of the latest insights into how cytoskeletal remodeling affects neuronal plasticity and discuss how the cytoskeleton is being targeted in an effort to promote plasticity and repair following traumatic injury in the central nervous system. This article is protected by copyright. All rights reserved.
    Journal of Neurochemistry 10/2013; 129(2). DOI:10.1111/jnc.12502 · 4.28 Impact Factor
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    • "The planes of PSD1, 2, and 3 are perpendicular, oblique, and parallel to this electron microscopic section, respectively. Reprinted from Mitsuyama et al. (2008) [21] with permission. Bar, 150 nm. "
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    ABSTRACT: There are many microtubules in axons and dendritic shafts, but it has been thought that there were fewer microtubules in spines. Recently, there have been four reports that observed the intraspinal microtubules. Because microtubules originate from the centrosome, these four reports strongly suggest a stimulation-dependent connection between the nucleus and the stimulated postsynaptic membrane by microtubules. In contrast, several pieces of evidence suggest that spine elongation may be caused by the polymerization of intraspinal microtubules. This structural mechanism for spine elongation suggests, conversely, that the synapse loss or spine loss observed in Alzheimer's disease may be caused by the depolymerization of intraspinal microtubules. Based on this evidence, it is suggested that the impairment of intraspinal microtubules may cause spinal structural change and block the translocation of plasticity-related molecules between the stimulated postsynaptic membranes and the nucleus, resulting in the cognitive deficits of Alzheimer's disease.
    International Journal of Alzheimer's Disease 03/2012; 2012(6):519682. DOI:10.1155/2012/519682
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    • "Such a notion, however, might be attributable to limited imaging techniques for capturing a small number of dynamic MTs entering the tiny actin-rich protrusions. Recent reports show the presence of microtubule structures in spines under certain conditions, such as strong tetanic stimulation to induce long-term potentiation (Mitsuyama et al., 2008), or during recovery from slice preparation (Fiala et al., 2003). It is thus conceivable to speculate that transient polymerization of microtubules in spines might contribute to spine regulation during plasticity (van Rossum and Hanisch, 1999). "
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    ABSTRACT: It is generally believed that only the actin cytoskeleton resides in dendritic spines and controls spine morphology and plasticity. Here, we report that microtubules (MTs) are present in spines and that shRNA knockdown of the MT plus-end-binding protein EB3 significantly reduces spine formation. Furthermore, stabilization and inhibition of MTs by low doses of taxol and nocodazole enhance and impair spine formation elicited by BDNF (brain-derived neurotrophic factor), respectively. Therefore, MTs play an important role in the control and regulation of dendritic spine development and plasticity.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 12/2008; 28(46):12120-4. DOI:10.1523/JNEUROSCI.2509-08.2008 · 6.34 Impact Factor
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