Rapid spine stabilization and synaptic enhancement at the onset of behavioral learning

Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Nature (Impact Factor: 41.46). 02/2010; 463(7283):948-52. DOI: 10.1038/nature08759
Source: PubMed


Behavioural learning depends on the brain's capacity to respond to instructive experience and is often enhanced during a juvenile sensitive period. How instructive experience acts on the juvenile brain to trigger behavioural learning remains unknown. In vitro studies show that forms of synaptic strengthening thought to underlie learning are accompanied by an increase in the stability, number and size of dendritic spines, which are the major sites of excitatory synaptic transmission in the vertebrate brain. In vivo imaging studies in sensory cortical regions reveal that these structural features can be affected by disrupting sensory experience and that spine turnover increases during sensitive periods for sensory map formation. These observations support two hypotheses: first, the increased capacity for behavioural learning during a sensitive period is associated with enhanced spine dynamics on sensorimotor neurons important for the learned behaviour; second, instructive experience rapidly stabilizes and strengthens these dynamic spines. Here we report a test of these hypotheses using two-photon in vivo imaging to measure spine dynamics in zebra finches, which learn to sing by imitating a tutor song during a juvenile sensitive period. Spine dynamics were measured in the forebrain nucleus HVC, the proximal site where auditory information merges with an explicit song motor representation, immediately before and after juvenile finches first experienced tutor song. Higher levels of spine turnover before tutoring correlated with a greater capacity for subsequent song imitation. In juveniles with high levels of spine turnover, hearing a tutor song led to the rapid ( approximately 24-h) stabilization, accumulation and enlargement of dendritic spines in HVC. Moreover, in vivo intracellular recordings made immediately before and after the first day of tutoring revealed robust enhancement of synaptic activity in HVC. These findings suggest that behavioural learning results when instructive experience is able to rapidly stabilize and strengthen synapses on sensorimotor neurons important for the control of the learned behaviour.

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    • "Within critical time periods, these excessive synapses are eliminated, whereas the remaining inputs are further strengthened to form the mature neural circuit (Shatz 1983; Sanes and Lichtman 1999). Synapse-elimination processes have also been observed during synaptic plasticity in the adult brain (Xu et al. 2009b; Yang et al. 2009; Roberts et al. 2010 "
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    ABSTRACT: Astrocytes, through their close associations with synapses, can monitor and alter synaptic function, thus actively controlling synaptic transmission in the adult brain. Besides their important role at adult synapses, in the last three decades a number of critical findings have highlighted the importance of astrocytes in the establishment of synaptic connectivity in the developing brain. In this article, we will review the key findings on astrocytic control of synapse formation, function, and elimination. First, we will summarize our current structural and functional understanding of astrocytes at the synapse. Then, we will discuss the cellular and molecular mechanisms through which developing and mature astrocytes instruct the formation, maturation, and refinement of synapses. Our aim is to provide an overview of astrocytes as important players in the establishment of a functional nervous system. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.
    Cold Spring Harbor perspectives in biology 02/2015; 7(9). DOI:10.1101/cshperspect.a020370 · 8.68 Impact Factor
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    • "Dendrite complexity and the morphologies of post-synaptic spines are critical components for learning and memory [37], [38]; therefore, we examined alterations in dendritic spines using Golgi staining. We found that the dendritic branches and mushroom-type spines in the hippocampus of ICV-STZ-treated rats decreased remarkably and that supplement treatment with magnesium sulfate almost fully reversed the number of dendritic branches and mushroom percentage (Fig. 3A–C). "
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    ABSTRACT: Alzheimer's disease (AD) is characterized by profound synapse loss and impairments of learning and memory. Magnesium affects many biochemical mechanisms that are vital for neuronal properties and synaptic plasticity. Recent studies have demonstrated that the serum and brain magnesium levels are decreased in AD patients; however, the exact role of magnesium in AD pathogenesis remains unclear. Here, we found that the intraperitoneal administration of magnesium sulfate increased the brain magnesium levels and protected learning and memory capacities in streptozotocin-induced sporadic AD model rats. We also found that magnesium sulfate reversed impairments in long-term potentiation (LTP), dendritic abnormalities, and the impaired recruitment of synaptic proteins. Magnesium sulfate treatment also decreased tau hyperphosphorylation by increasing the inhibitory phosphorylation of GSK-3β at serine 9, thereby increasing the activity of Akt at Ser473 and PI3K at Tyr458/199, and improving insulin sensitivity. We conclude that magnesium treatment protects cognitive function and synaptic plasticity by inhibiting GSK-3β in sporadic AD model rats, which suggests a potential role for magnesium in AD therapy.
    PLoS ONE 09/2014; 9(9):e108645. DOI:10.1371/journal.pone.0108645 · 3.23 Impact Factor
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    • "Dendryt z kolcami dendrycznymi oznaczono czarnym kolorem, akson – białym. liczba, kształt i rozmiar potrafi się znacznie zmieniać w krótkim czasie, nawet u dorosłych osób zaobserwowano istotne zmiany strukturalne na przestrzeni kilku godzin (Roberts i in., 2010). Żywotność oraz metabolizm kolców są ściśle powiązane z intensywnością pobudzających je bodźców (De Roo i in., 2008b). "
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    ABSTRACT: Understanding how nervous cells encode and decode information, process it, and control its transmission, is one of the greatest challenges of the contemporary science. Experiments have shown that information transmitted between neurons is represented by action potentials, i.e electrical impulses in form of short, sharp cell membrane voltage spikes of similar amplitude. For many years, method of coding these signals by neurons is subject of increased effort among researchers around the world. The purpose of research presented here is, first, to develop methods based on information theory and numerical tools, that allow effective determination optimal parameters (including energetic costs) of neuronal information transmission and to examine effects of synergy of cooperating cells in terms of transmission efficiency and reliability. Second, using obtained results and methods, to describe, in both quantitative and qualitative way, simplified brain model, so called brain–like, built of neurons considered earlier. A nonclassical approach to neural networks is taken in the research: non-deterministic cells are considered, based on neuron model proposed by Levy & Baxter (2002). Networks are studied as a communication channels (Shannon, 1948). Therefore, among examined quantities are such as: channel capacity, transmission redundancy, mutual information between input signals (stimuli) and cell response (excitation), and energetic costs of communication. This requires optimal implementation of calculation-expensive entropy estimators. Thus, Strong (1998) estimator is chosen. First, single neurons and feed–forward networks are examined. Optimal information transmission is analyzed in regard to changes of firing rates, synaptic noise and height of activation threshold. Influence of different information source types is also described, as well as impact of amplitude fluctuations. Next, brain–like networks are studied. Information transmission efficiency of excitatory neurons is analyzed as a function of: geometrical size of network (and size-related communication delays), inhibition strength, information source accessibility and additional long–range connections. Conducted computer calculations are accurate and precise. Input sequences used in simulations are at least 106 bits long – as opposed to experimental data, much shorter due to biological restrictions.
    09/2014, Degree: PhD, Supervisor: Janusz Szczepański
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