Tyler WJ, Alonso M, Bramham CR, Pozzo-Miller LD. From acquisition to consolidation: on the role of brain-derived neurotrophic factor signaling in hippocampal-dependent learning. Learn Mem 9: 224-237

Departments of Neurobiology and Psychology, Civitan International Research Center, University of Alabama at Birmingham, Birmingham, Alabama 35294-0021, USA.
Learning &amp Memory (Impact Factor: 3.66). 09/2002; 9(5):224-37. DOI: 10.1101/lm.51202
Source: PubMed


One of the most rigorously investigated problems in modern neuroscience is to decipher the mechanisms by which experience-induced changes in the central nervous system are translated into behavioral acquisition, consolidation, retention, and subsequent recall of information. Brain-derived neurotrophic factor (BDNF) has recently emerged as one of the most potent molecular mediators of not only central synaptic plasticity, but also behavioral interactions between an organism and its environment. Recent experimental evidence indicates that BDNF modulates synaptic transmission and plasticity by acting across different spatial and temporal domains. BDNF signaling evokes both short- and long-term periods of enhanced synaptic physiology in both pre- and postsynaptic compartments of central synapses. Specifically, BDNF/TrkB signaling converges on the MAP kinase pathway to enhance excitatory synaptic transmission in vivo, as well as hippocampal-dependent learning in behaving animals. Emerging concepts of the intracellular signaling cascades involved in synaptic plasticity induced through environmental interactions resulting in behavioral learning further support the contention that BDNF/TrkB signaling plays a fundamental role in mediating enduring changes in central synaptic structure and function. Here we review recent literature showing the involvement of BDNF/TrkB signaling in hippocampal-dependent learning paradigms, as well as in the types of cellular plasticity proposed to underlie learning and memory.

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Available from: Lucas Pozzo-Miller, Dec 17, 2013
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    • "These cognitive impairments are paralleled by decreased BDNF mRNA in the hippocampus of antibiotic-treated mice, a finding that correlates with previous reports in GF mice (Diaz Heijtz et al., 2011; Clarke et al., 2013; Gareau et al., 2011). The neuroprotective role of BDNF in the brain, and the association between altered levels in the hippocampus and learning and memory performance is well established (Mizuno et al., 2000; Tyler et al., 2002; Baj et al., 2013). It is still unclear how compositional changes in the gut microbiota induce changes in brain expression of BDNF, or indeed, in anxiety and cognition. "
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    ABSTRACT: There is growing appreciation for the importance of bacteria in shaping brain development and behaviour. Adolescence and early adulthood are crucial developmental periods during which exposure to harmful environmental factors can have a permanent impact on brain function. Such environmental factors include perturbations of the gut bacteria that may affect gut-brain communication, altering the trajectory of brain development, and increasing vulnerability to psychiatric disorders. Here we assess the effects of gut bacterial depletion from weaning onwards on adult cognitive, social and emotional behaviours and markers of gut-brain axis dysfunction in mice. Mice were treated with a combination of antibiotics from weaning onwards and effects on behaviours and potential brain-gut axis neuromodulators (tryptophan, monoamines, and neuropeptides) and BDNF expression were assessed in adulthood. Antibiotic-treatment depleted and restructured gut microbiota composition of caecal contents and decreased spleen weights in adulthood. Depletion of the gut microbiota from weaning onwards reduced anxiety, induced cognitive deficits, altered dynamics of the tryptophan metabolic pathway, and significantly reduced BDNF, oxytocin and vasopressin expression in the adult brain. Microbiota depletion from weaning onwards by means of chronic treatment with antibiotics in mice impacts on anxiety and cognitive behaviours as well as key neuromodulators of gut-brain communication in a manner that is similar to that reported in germ-free mice. This model may represent a more amenable alternative for germ-free mice in the assessment of microbiota modulation of behaviour. Finally, these data suggest that despite the presence of a normal gut microbiome in early postnatal life, reduced abundance and diversity of the gut microbiota from weaning influences adult behaviours and key neuromodulators of the microbiota-gut-brain axis suggesting that dysregulation of this axis in the post-weaning period may contribute to the pathogenesis of disorders associated with altered anxiety and cognition. Copyright © 2015. Published by Elsevier Inc.
    Brain Behavior and Immunity 04/2015; 48. DOI:10.1016/j.bbi.2015.04.004 · 5.89 Impact Factor
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    • "Notably, TRPC3 channels have been described as mediators of BDNF-mediated dendritic remodeling in hippocampal CA1 pyramidal neurons [141]. BDNF plays a significant role in modulating synaptic plasticity (reviewed in [142]) by enhancing synaptic transmission at excitatory synapses and altering dendritic architecture [143]. The role of interactions between STIM1 proteins and TRPC channels is under vigorous investigation (reviewed in [73]). "
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    ABSTRACT: In this review we describe the present knowledge about store operated Ca2 + entry (SOCE) in neurons and the proteins involved in this process: STIM, as well as Orai and TRP channels. We address the issue of whether SOCE is used only to refill Ca2 + in the ER or whether Ca2 + that enters the neuronal cell during SOCE also performs signaling functions. We collected the data indicating that SOCE and its components participate in the important processes in neurons. This has implications for identifying new drug targets for the treatment of brain diseases. Evidence indicates that in neurodegenerative diseases Ca2 + homeostasis and SOCE components become dysregulated. Thus, different targets and strategies might be identified for the potential treatment of these diseases. This article is part of a Special Issue entitled: 13th European Symposium on Calcium.
    Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 01/2015; 740(9). DOI:10.1016/j.bbamcr.2015.01.019 · 5.02 Impact Factor
    • "BDNF can also be neuroprotective, mitigating the damaging effects of a variety of insults. In addition, BDNF plays a central role in forms of long-lasting synaptic plasticity associated with consolidation of hippocampus-dependent memory (Bramham and Messaoudi, 2005; Lu, 2003; Tyler et al., 2002) e the same memory-related plasticity processes compromised by excessive IL-1b. The capacity to produce BDNF is generally very tightly controlled. "
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    ABSTRACT: Older individuals often experience declines in cognitive function after events (e.g. infection, or injury) that trigger activation of the immune system. This occurs at least in part because aging sensitizes the response of microglia (the brain's resident immune cells) to signals triggered by an immune challenge. In the aging brain, microglia respond to these signals by producing more pro-inflammatory cytokines (e.g. interleukin-1beta or IL-1β) and producing them for longer than microglia in younger brains. This exaggerated inflammatory response can compromise processes critical for optimal cognitive functioning. Interleukin-1β is central to the inflammatory response and is a key mediator and modulator of an array of associated biological functions; thus its production and release is usually very tightly regulated. This review will focus on the impact of dysregulated production of IL-1β on hippocampus dependent-memory systems and associated synaptic plasticity processes. The neurotrophin brain-derived neurotrophic factor (BNDF) helps to protect neurons from damage caused by caused by infection or injury, and it plays a critical role in many of the same hippocampal plasticity and memory processes compromised by dysregulated production of IL-1β. This suggests that an exaggerated brain inflammatory response, arising from aging and a secondary immune challenge, may erode the capacity to provide the BDNF needed for memory-related plasticity processes at hippocampal synapses. Copyright © 2014. Published by Elsevier Ltd.
    Neuropharmacology 12/2014; 96(Pt A). DOI:10.1016/j.neuropharm.2014.12.020 · 5.11 Impact Factor
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