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Molecule to Cognition unit
Bong-Kiun Kaang, Dept of Biological Sciences, SNU HP
2010
* Detection of TrkB Receptors Distributed in Cultured Hippocampal Neurons through Bioconjugation between Highly Luminescent (Quantum Dot-Neutravidin) and (Biotinylated Anti-TrkB Antibody) on Neurons by Combined Atomic Force Microscope and Confocal Laser Scanning Microscope.
[Pubmed] [PDF]
We developed highly luminescent and cost-effective quantum dot (QD)-neutravidin (NTV) bioconjugates to detect the tyrosine kinase B (TrkB) receptors distributed in the cultured hippocampus neurons. Hippocampal neurons were incubated with biotinylated anti-TrkB antibody, followed by further incubation with QD-NTV bioconjugates. QD-NTV biomarkers on the extracellular domain of TrkB receptors were imaged by the combined atomic force microscope and confocal laser scanning microscope (AFM-CLSM) providing resolved (nanometer-scale) structural and fluorescent images. We found that TrkB receptors were distributed over the neuronal cell bodies (soma) and neurites. TrkB receptors in the somata looked more concentrated, but those in the neurites appeared punctate. Thus, our QD-based immunocytochemistry technique combined with an AFM-CLSM can be used for threedimensional morphology of neurons on nanometer-scale structural resolution and their fluorescence images with QDs. Furthermore, this technique can be applied for real-time fluorescence imaging or long-term study of live neurons.
* Neuronal RNA granule contains ApCPEB1, a novel Aplysia CPEB, in Aplysia sensory neuron.
[Pubmed] [PDF]
The cytoplasmic polyadenylation element (CPE)-binding protein (CPEB) binds to CPE containing mRNAs on their 3' untranslated regions (3'UTRs). This RNA binding protein comes out many important tasks, especially in learning and memory, by modifying the translational efficiency of target mRNAs via poly (A) tailing. Overexpressed CPEB has been reported to induce the formation of stress granules (SGs), a sort of RNA granule in mammalian cell lines. RNA granule is considered to be a potentially important factor in learning and memory. However, there is no study about RNA granule in Aplysia. To examine whether an Aplysia CPEB, ApCPEB1, forms RNA granules, we overexpressed ApCPEB1-EGFP in Aplysia sensory neurons. Consistent with the localization of mammalian CPEB, overexpressed ApCPEB1 formed granular structures, and was colocalized with RNAs and another RNA binding protein, ApCPEB, showing that ApCPEB1 positive granules are RNA-protein complexes. In addition, ApCPEB1 has a high turnover rate in RNA granules which were mobile structures. Thus, our results indicate that overexpressed ApCPEB1 is incorporated into RNA granule which is a dynamic structure in Aplysia sensory neuron. We propose that ApCPEB1 granule might modulate translation, as other RNA granules do, and furthermore, influence memory.
* Protein synthesis and degradation are required for the incorporation of modified information into the pre-existing object-location memory.
[Pubmed] [PDF]
Although some reports indicate that protein synthesis dependent process may be induced by updating information, the role of protein synthesis and degradation in changing the content of pre-existing memory is yet unclear. In this study, we utilized an object rearrangement task, in which partial information related to a pre-existing memory is changed, promoting memory modification. Inhibitors of both protein synthesis and protein degradation impaired adequate incorporation of the altered information, each in a distinctive way. These results indicate that protein synthesis and degradation play key roles in memory modification.
2009
* Social Isolation Selectively Increases Anxiety in Mice without Affecting Depression-like Behavior.
[Pubmed] [PDF]
It is hypothesized that a number of environmental factors affect animals’ behavior. Without controlling these variables, it is very hard for researchers to get not only reliable, but replicable data from various behavioral experiments testing animals’ cognitive as well as emotional functions. For example, laboratory mice which had restricted environment showed different synaptic potentiation properties with wild mice (Zhao MG et al., 2009). While performing behavioral experiments, however, it is sometimes inevitable that the researcher changes the animals’ environments, as by switching the cages in which experimental animals are housed and separating animals raised together into small experimental groups. In this study, we investigated the effect of environmental changes on mice’s emotional behaviors by socially isolating them or reducing the size of their cage. We found that social isolation selectively increases the animals' levels of anxiety, while leaving depression-like behaviors unchanged. On the other hand, alteration of the housing dimensions affected neither their anxiety levels nor their depression-like behaviors. These results suggest that environmental variables may have a prominent impact on experimental animals’ emotional behaviors and possibly their psychological states, leading to bias in the behavioral data produced from experiments. Key Words: Anxiety level, Social isolation, Housing environment, Experimental animals, Open field test, Tail suspension test, Forced swim test
* Effects of Protease Treatment and Animal Behavior on the Dissociative Culture of Aplysia Neurons.
[Pubmed] [PDF]
The dissociative culture technique of Aplysia neuron is one of the key methods that have been used for studies of cellular and molecular mechanisms of neuronal functioning. However, despite the advantages this method offers as an experimental model, its technical efficiency has had room for improvement. In this study, we examined certain putative factors that might affect the culture quality. The effects of neuronal damage induced by physical injuries, heat shock, and surface protein degradation were evaluated along with the correlation between the culture quality and animal behavior. As a result, we found that physical injury can be a critical factor that affects culture quality, whereas the heat shock and surface protein degradation had negligible effect on it. In addition, we discovered that siphon retraction time was not a good measurement for healthy neurons. Based on these findings, we suggest here an improved method in which the degree of physical injury is reduced by means of multiple protease treatment.
* Identification of a serotonin receptor coupled to adenylyl cyclase involved in learning-related heterosynaptic facilitation in Aplysia.
[Pubmed] [PDF]
Serotonin (5-HT) plays a critical role in modulating synaptic plasticity in the marine mollusc Aplysia and in the mammalian nervous system. In Aplysia sensory neurons, 5-HT can activate several signal cascades, including PKA and PKC, presumably via distinct types of G proteincoupled receptors. However, the molecular identities of these receptors have not yet been identified. We here report the cloning and functional characterization of a 5-HT receptor that is positively coupled to adenylyl cyclase in Aplysia neurons. The cloned receptor, 5-HTapAC1, stimulates the production of cAMP in HEK293T cells and in Xenopus oocytes. Moreover, the knockdown of 5-HTapAC1 expression by RNA interference blocked 5-HT-induced cAMP production in Aplysia sensory neurons and blocked synaptic facilitation in nondepressed or partially depressed sensory-to-motor neuron synapses. These data implicate 5-HTapAC1 as a major modulator of learning related synaptic facilitation in the direct sensory to motor neuron pathway of the gill withdrawal reflex.
* Transcriptome and protein domain analyses in Aplysia nervous system with evolutionary implications.
[Pubmed] [PDF]
The sea hare Aplysia is a powerful model organism for studying the structure and function of the nervous system. Recently, the genomic characterization of Aplysia has been facilitated: A large scale EST sequences was acquired by sequencing cDNA libraries from A. californica and a parallel EST database of the closely related species A. kurodai was reported. These EST databases provide useful tools for both molecular biology and bioinformatics. In our previous report, we demonstrated the utility of the database by screening the candidate genes for the synaptic plasticity and the behavioral sensitization using the microarray containing A. kurodai ESTs. In this addendum, we have expanded our study to show that the protein domain repertoire and the abundance of regulatory genes displayed a linear relationship with the evolution of the complex brains in different lineages. This distinct set of protein domains may play critical roles in evolution of the nervous systems.
* Induction of neuronal vascular endothelial growth factor expression by cAMP in the dentate gyrus of the hippocampus is required for antidepressant-like behaviors.
[Pubmed] [PDF]
The cAMP cascade and vascular endothelial growth factor (VEGF) are critical modulators of depression. Here we have tested whether the antidepressive effect of the cAMP cascade is mediated by VEGF in the adult hippocampus.Weused a conditional genetic system in which the Aplysia octopamine receptor (Ap oa1), a Gs-coupled receptor, is transgenically expressed in the forebrain neurons of mice. Chronic activation of the heterologous Ap oa1 by its natural ligand evoked antidepressant-like behaviors, accompanied by enhanced phosphorylation of cAMP response element-binding protein and transcription of VEGF in hippocampal dentate gyrus (DG) neurons. Selective knockdown of VEGF in these cells during the period of cAMP elevation inhibited the antidepressant-like behaviors. These findings reveal a molecular interaction between the cAMP cascade and VEGF expression, and the pronounced behavioral consequences of this interaction shed light on the mechanism underlying neuronal VEGF functions in antidepression.
* Two major gate-keepers in the self-renewal of neural stem cells: Erk1/2 and PLCgamma1 in FGFR signaling.
[Pubmed] [PDF]
An accumulating body of evidence shows that reactivated long-term memory undergoes a dynamic process called reconsolidation, in which de novo protein synthesis is required to maintain the memory. These findings open up a new dimension in the field of memory research. However, few studies have shown how once-consolidated memory becomes labile. The authors’ recent findings have demonstrated that preexisting long-term memory becomes unstable via the ubiquitin/ proteasome-dependent protein degradation pathway and that this labile state is required for the reorganization of fear memory. Here, the authors review this finding and focus on the labile state that is critical for the reorganization
* Synaptic Protein Degradation as a Mechanism in Memory Reorganization.
[Pubmed] [PDF]
Neural stem cells are undifferentiated precursor cells that proliferate, self-renew, and give rise to neuronal and glial lineages. Understanding the molecular mechanisms underlying their self-renewal is an important aspect in neural stem cell biology. The regulation mechanisms governing self-renewal of neural stem cells and the signaling pathways responsible for the proliferation and maintenance of adult stem cells remain largely unknown. In this issue of Molecular Brain [Ma DK et al. Molecular genetic analysis of FGFR1 signaling reveals distinct roles of MAPK and PLC1 activation for self-renewal of adult neural stem cells. Molecular Brain 2009, 2:16], characterized the different roles of MAPK and PLC1 in FGFR1 signaling in the self-renewal of neural stem cells. These novel findings provide insights into basic neural stem cell biology and clinical applications of potential stem-cell-based therapy.
* The role of lipid binding for the targeting of synaptic proteins into synaptic vesicles.
[Pubmed] [PDF]
An accumulating body of evidence shows that reactivated long-term memory undergoes a dynamic process called reconsolidation, in which de novo protein synthesis is required to maintain the memory. These findings open up a new dimension in the field of memory research. However, few studies have shown how once-consolidated memory becomes labile. The authors’ recent findings have demonstrated that preexisting long-term memory becomes unstable via the ubiquitin/ proteasome-dependent protein degradation pathway and that this labile state is required for the reorganization of fear memory. Here, the authors review this finding and focus on the labile state that is critical for the reorganization
* Effect of ablated hippocampal neurogenesis on the formation and extinction of contextual fear memory.
[Pubmed] [PDF]
Newborn neurons in the subgranular zone (SGZ) of the hippocampus incorporate into the dentate gyrus and mature. Numerous studies have focused on hippocampal neurogenesis because of its importance in learning and memory. However, it is largely unknown whether hippocampal neurogenesis is involved in memory extinction per se. Here, we sought to examine the possibility that hippocampal neurogenesis may play a critical role in the formation and extinction of hippocampus-dependent contextual fear memory. By methylazoxymethanol acetate (MAM) or gamma-ray irradiation, hippocampal neurogenesis was impaired in adult mice. Under our experimental conditions, only a severe impairment of hippocampal neurogenesis inhibited the formation of contextual fear memory. However, the extinction of contextual fear memory was not affected. These results suggest that although adult newborn neurons contribute to contextual fear memory, they may not be involved in the extinction or erasure of hippocampus-dependent contextual fear memory.
Graham Leon Collingridge FRS, MRC Centre for Synaptic Plasticity, U of Bristol HP
2010
* Disruption of the interaction between myosin VI and SAP97 is associated with a reduction in the number of AMPARs at hippocampal synapses 2010.[Article (PDF)]
2009
* A systematic investigation of the protein kinases involved in NMDA receptor-dependent LTD: evidence for a role of GSK-3 but not other serine/threonine kinases[Abstract] [Full Text] [PDF] [PubMed] [Related articles] [Cited on BioMed Central]
* A novel mechanism of hippocampal LTD involving muscarinic receptor-triggered interactions between AMPARs, GRIP and liprin-α
[Abstract] [Full Text] [PDF] [PubMed] [Related articles] [Cited on BioMed Central]
Min Zhuo, Dept of Physiology, U of Toronto HP
2010
* CaMKIV forebrain overexpression boosts cortical 4-7Hz oscillations during learning and 1-4Hz delta oscillations during sleep[Abstract] [PubMed] [Related articles]
* DREAM (Downstream Regulatory Element Antagonist Modulator) contributes to synaptic depression and contextual fear memory
[Abstract] [Full Text] [PubMed] [Related articles]
2009
* Enhanced synaptic long-term potentiation in the anterior cingulate cortex of adult wild mice as compared with that in laboratory mice[Abstract] [Full Text] [PubMed] [Related articles]
* Sexual attraction enhances glutamate transmission in mammalian anterior cingulate cortex
[Abstract] [Full Text] [PubMed] [Related articles] [Cited on BioMed Central]
* Plasticity of NMDA receptor NR2B subunit in memory and chronic pain
[Abstract] [Full Text] [PubMed] [Related articles] [Cited on BioMed Central]
