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Raz Yirmiya - One of the best experts on this subject based on the ideXlab platform.

  • Microglia and their CX3CR1 signaling are involved in hippocampal- but not olfactory bulb-related Memory and neurogenesis
    Brain behavior and immunity, 2014
    Co-Authors: R. Reshef, Tirzah Kreisel, Dorsa Beroukhim Kay, Raz Yirmiya
    Abstract:

    Recent studies demonstrate that microglia play an important role in cognitive and neuroplasticity processes, at least partly via microglial CX3C receptor 1 (CX3CR1) signaling. Furthermore, microglia are responsive to environmental enrichment (EE), which modulates learning, Memory and neurogenesis. In the present study we examined the role of microglial CX3CR1 signaling in hippocampal- and olfactory-bulb (OB)-related Memory and neurogenesis in homozygous mice with microglia-specific transgenic expression of GFP under the CX3CR1 promoter (CX3CR1(-/-) mice), in which the CX3CR1 gene is functionally deleted, as well as heterozygous CX3CR1(+/-) and WT controls. We report that the CX3CR1-deficient mice displayed better Hippocampal-Dependent Memory functioning and olfactory recognition, along with increased number and soma size of hippocampal microglia, suggestive of mild activation status, but no changes in OB microglia. A similar increase in Hippocampal-Dependent Memory functioning and microglia number was also induced by pharmacological inhibition of CX3CR1 signaling, using chronic (2weeks) i.c.v. administration of CX3CR1 blocking antibody. In control mice, EE improved Hippocampal-Dependent Memory and neurogenesis, and increased hippocampal microglia number and soma size, whereas odor enrichment (OE) improved olfactory recognition and OB neurogenesis without changing OB microglia status. In CX3CR1-deficient mice, EE and OE did not produce any further improvement in Memory functioning or neurogenesis and had no effect on microglial status. These results support the notion that in the hippocampus microglia and their interactions with neurons via the CX3CR1 play an important role in Memory functioning and neurogenesis, whereas in the OB microglia do not seem to be involved in these processes.

  • microglia and their cx3cr1 signaling are involved in hippocampal but not olfactory bulb related Memory and neurogenesis
    Brain Behavior and Immunity, 2013
    Co-Authors: R. Reshef, Tirzah Kreisel, Raz Yirmiya
    Abstract:

    Recent studies suggest that microglia are responsive to environmental conditions and modulate the alterations in neurogenesis induced by environmental enrichment (EE), possibly via the CX3C receptor (CX3CR1), which mediates neuro–microglial interactions. We examined the role of microglia and CX3CR1 signaling in hippocampal- and olfactory bulb (OB)-related Memory and neurogenesis in heterozygous mice with microglia-specific transgenic expression of GFP under the CX3CR1 promoter (CX3CR1+/− mice) as well as homozygous CX3CR1-/- mice, in which the CX3CR1 gene is functionally deleted. CX3CR1−/− mice displayed better functioning in Hippocampal-Dependent Memory tasks and in olfactory recognition compared with CX3CR1+/− mice. In CX3CR1+/− mice, EE improved Hippocampal-Dependent Memory and neurogenesis, and odor enrichment (OE) improved olfactory recognition and neurogenesis, however neither EE nor OE further improved Memory functioning or neurogenesis in CX3CR1−/− mice. Consistently, compared with non-enriched CX3CR1+/− mice, CX3CR1−/− and EE CX3CR1+/− mice displayed greater numbers of dentate gyrus microglia and increased soma size, suggesting mild activation status. In contrast, the number and morphology of microglia in the OB of CX3CR1−/− mice was comparable to that in CX3CR1+/− mice, and it was not altered by OE in either strain. These results support the notion that in the hippocampus microglia and their interactions with neurons via the CX3CR1 play an important role in Memory functioning and neurogenesis, whereas in the OB microglia do not seem to be involved in these functions.

  • Astrocytes support Hippocampal-Dependent Memory and long-term potentiation via interleukin-1 signaling.
    Brain behavior and immunity, 2010
    Co-Authors: Ofra Ben Menachem-zidon, Inbal Goshen, Tirzah Kreisel, Avi Avital, Yair Ben-menahem, Eli M. Shmueli, Menahem Segal, Tamir Ben Hur, Raz Yirmiya
    Abstract:

    Recent studies indicate that astrocytes play an integral role in neural and synaptic functioning. To examine the implications of these findings for neurobehavioral plasticity we investigated the involvement of astrocytes in Memory and long-term potentiation (LTP), using a mouse model of impaired learning and synaptic plasticity caused by genetic deletion of the interleukin-1 receptor type I (IL-1RI). Neural precursor cells (NPCs), derived from either wild type (WT) or IL-1 receptor knockout (IL-1rKO) neonatal mice, were labeled with bromodeoxyuridine (BrdU) and transplanted into the hippocampus of either IL-1rKO or WT adult host mice. Transplanted NPCs survived and differentiated into astrocytes (expressing GFAP and S100β), but not to neurons or oligodendrocytes. The NPCs-derived astrocytes from WT but not IL-1rKO mice displayed co-localization of GFAP with the IL-1RI. Four to twelve weeks post-transplantation, Memory functioning was examined in the fear-conditioning and the water maze paradigms and LTP of perforant path-dentate gyrus synapses was assessed in anesthetized mice. As expected, IL-1rKO mice transplanted with IL-1rKO cells or sham operated displayed severe Memory disturbances in both paradigms as well as a marked impairment in LTP. In contrast, IL-1rKO mice transplanted with WT NPCs displayed a complete rescue of the impaired Memory functioning as well as partial restoration of LTP. These findings indicate that astrocytes play a critical role in Memory functioning and LTP, and specifically implicate astrocytic IL-1 signaling in these processes. The results suggest novel conceptualization and therapeutic targets for neuropsychiatric disorders characterized by impaired astrocytic functioning concomitantly with disturbed Memory and synaptic plasticity.

  • A dual role for interleukin-1 in Hippocampal-Dependent Memory processes.
    Psychoneuroendocrinology, 2007
    Co-Authors: Inbal Goshen, Tirzah Kreisel, Hadile Ounallah-saad, Paul Renbaum, Yael Zalzstein, Tamir Ben-hur, Efrat Levy-lahad, Raz Yirmiya
    Abstract:

    Ample research demonstrates that pathophysiological levels of the pro-inflammatory cytokine interleukin-1 (IL-1) produces detrimental effects on Memory functioning. However, recent evidence suggests that IL-1 may be required for the normal physiological regulation of Hippocampal-Dependent Memory. To substantiate the physiological role of IL-1 in learning and Memory we examined the induction of IL-1 gene expression following a learning experience, and the effects of IL-1 signaling blockade, by either genetic or pharmacological manipulations, on Memory functioning. We show that IL-1 gene expression is induced in the hippocampus 24h following fear-conditioning in wild type mice, but not in two mouse strains with impaired IL-1 signaling. Moreover, we report that mice with transgenic over-expression of IL-1 receptor antagonist restricted to the CNS (IL-1raTG) display impaired Hippocampal-Dependent and intact hippocampal-independent Memory in the water maze and fear-conditioning paradigms. We further demonstrate that continuous administration of IL-1ra via osmotic minipumps during prenatal development disrupt Memory performance in adult mice, suggesting that IL-1 plays a critical role not only in the formation of Hippocampal-Dependent Memory but also in normal hippocampal development. Finally, we tested the dual role of IL-1 in Memory by intracerebroventricular (ICV) administration of different doses of IL-1beta and IL-1ra following learning, providing the first systematic evidence that the involvement of IL-1 in Hippocampal-Dependent Memory follows an inverted U-shaped pattern, i.e., a slight increase in brain IL-1 levels can improve Memory, whereas any deviation from the physiological range, either by excess elevation in IL-1 levels or by blockade of IL-1 signaling, results in impaired Memory.

Zhongyuan Xia - One of the best experts on this subject based on the ideXlab platform.

  • rem sleep deprivation induced circadian clock gene abnormalities participate in hippocampal dependent Memory impairment by enhancing inflammation in rats undergoing sevoflurane inhalation
    Behavioural Brain Research, 2019
    Co-Authors: Jiabao Hou, Qianni Shen, Xing Wan, Bo Zhao, Zhongyuan Xia
    Abstract:

    Sleep disturbance can result in Memory impairment, and both sleep and hippocampal Memory formation are maintained by circadian clock genes. Although preoperative sleep deprivation is known to be an independent risk factor for postoperative cognitive dysfunction (POCD) after inhalation anesthesia, the circadian mechanisms involved are currently unclear. To examine this issue, we constructed models of rapid eye movement sleep deprivation (RSD) and POCD after sevoflurane inhalation, to evaluate the circadian mechanisms underlying preoperative sleep deprivation-induced POCD after sevoflurane inhalation. Morris water maze probe test performance revealed that RSD aggravated the Hippocampal-Dependent Memory impairment induced by sevoflurane anesthesia, and the recovery period of Memory impairment was prolonged for more than a week by sleep deprivation. Western blot analysis revealed that sleep deprivation inhibited hippocampal Bmal1 and Egr1 expression for more than 7 days after sevoflurane inhalation. Importantly, hippocampal Per2 expression levels were first decreased by sevoflurane inhalation then increased from the third day by sleep deprivation. Sleep deprivation enhanced the expression of hippocampal inflammatory factors IL-1β and IL-6 after sevoflurane inhalation. In addition, sevoflurane inhalation activated the plasma expression of S100β and IL-6, particularly after sleep deprivation. Sleep deprivation aggravated pathogenic impairment of pyramidal neurons and activated astrocytes in CA1 after sevoflurane inhalation. These results suggest that preoperative RSD aggravates hippocampal Memory impairment by enhancing neuroinflammatory injuries after sevoflurane inhalation, which is related to hippocampal clock gene abnormalities.

David Dupret - One of the best experts on this subject based on the ideXlab platform.

  • dopaminergic neurons promote hippocampal reactivation and spatial Memory persistence
    Nature Neuroscience, 2014
    Co-Authors: Colin G Mcnamara, Alvaro Tejerocantero, Stephanie Trouche, Natalia Campourriza, David Dupret
    Abstract:

    In this study, the authors show that optogenetic photostimulation of dopaminergic (DA) neurons in the ventral tegmental area during exploration can enhance subsequent sharp wave/ripple-mediated reactivation of spatial Memory. These results suggest that midbrain DA neurons are key mediators of Hippocampal-Dependent Memory persistence.

  • Dopaminergic neurons promote hippocampal reactivation and spatial Memory persistence
    Nature Neuroscience, 2014
    Co-Authors: Colin G Mcnamara, Stephanie Trouche, Álvaro Tejero-cantero, Natalia Campo-urriza, David Dupret
    Abstract:

    We found that optogenetic burst stimulation of hippocampal dopaminergic fibers from midbrain neurons in mice exploring novel environments enhanced the reactivation of pyramidal cell assemblies during subsequent sleep/rest. When applied during spatial learning of new goal locations, dopaminergic photostimulation improved the later recall of neural representations of space and stabilized Memory performance. These findings reveal that midbrain dopaminergic neurons promote hippocampal network dynamics associated with Memory persistence. In this study, the authors show that optogenetic photostimulation of dopaminergic (DA) neurons in the ventral tegmental area during exploration can enhance subsequent sharp wave/ripple-mediated reactivation of spatial Memory. These results suggest that midbrain DA neurons are key mediators of Hippocampal-Dependent Memory persistence.

Eric R. Kandel - One of the best experts on this subject based on the ideXlab platform.

  • Neuralized1 activates CPEB3: a function for nonproteolytic ubiquitin in synaptic plasticity and Memory storage.
    Cell, 2011
    Co-Authors: Elias Pavlopoulos, Pierre Trifilieff, Vivien Chevaleyre, Luana Fioriti, Sakellarios Zairis, Andrew M. Pagano, Gaël Malleret, Eric R. Kandel
    Abstract:

    The cytoplasmic polyadenylation element-binding protein 3 (CPEB3), a regulator of local protein synthesis, is the mouse homolog of ApCPEB, a functional prion protein in Aplysia. Here, we provide evidence that CPEB3 is activated by Neuralized1, an E3 ubiquitin ligase. In hippocampal cultures, CPEB3 activated by Neuralized1-mediated ubiquitination leads both to the growth of new dendritic spines and to an increase of the GluA1 and GluA2 subunits of AMPA receptors, two CPEB3 targets essential for synaptic plasticity. Conditional overexpression of Neuralized1 similarly increases GluA1 and GluA2 and the number of spines and functional synapses in the hippocampus and is reflected in enhanced Hippocampal-Dependent Memory and synaptic plasticity. By contrast, inhibition of Neuralized1 reduces GluA1 and GluA2 levels and impairs Hippocampal-Dependent Memory and synaptic plasticity. These results suggest a model whereby Neuralized1-dependent ubiquitination facilitates hippocampal plasticity and Hippocampal-Dependent Memory storage by modulating the activity of CPEB3 and CPEB3-dependent protein synthesis and synapse formation.

  • restricted and regulated overexpression reveals calcineurin as a key component in the transition from short term to long term Memory
    Cell, 1998
    Co-Authors: Isabelle M Mansuy, Eric R. Kandel, Mark Mayford, Betsy Jacob, Mary Elizabeth Bach
    Abstract:

    To investigate the roles phosphatases play in Hippocampal-Dependent Memory, we studied transgenic mice overexpressing a truncated form of calcineurin. These mice have normal short-term Memory but defective long-term Memory evident on both a spatial task and on a visual recognition task, providing genetic evidence for the role of the rodent hippocampus in spatial and nonspatial Memory. The defect in long-term Memory could be fully rescued by increasing the number of training trials, suggesting that the mice have the capacity for long-term Memory. We next analyzed mice overexpressing calcineurin in a regulated manner and found the Memory defect is reversible and not due to a developmental abnormality. Our behavioral results suggest that calcineurin has a role in the transition from short- to long-term Memory, which correlates with a novel intermediate phase of LTP.

  • impairment of spatial but not contextual Memory in camkii mutant mice with a selective loss of hippocampal ltp in the range of the θ frequency
    Cell, 1995
    Co-Authors: Mary Elizabeth Bach, Eric R. Kandel, Robert D Hawkins, Mona Osman, Mark Mayford
    Abstract:

    We assessed Hippocampal-Dependent Memory in mice with a Ca(2+)-independent form of CaMKII generated by the introduction of an aspartate at amino acid 286. The CaMKII-Asp-286 mice show normal LTP at high frequency stimulation, but in the 5-10 Hz range, they show a shift in the frequency-response curve favoring LTD. This range of frequencies is similar to the theta rhythm, which is associated with exploration in rodents. Using the Barnes maze to assess spatial Memory, we found the transgenic mice could not learn to navigate to a specific location using spatial cues. In contrast, one line of transgenic mice performed normally in contextual fear conditioning, a task that is also hippocampal dependent. This dissociation between spatial and contextual Memory suggests that even though both require the hippocampus, they may be mediated by different synaptic mechanisms.

Mary Elizabeth Bach - One of the best experts on this subject based on the ideXlab platform.

  • restricted and regulated overexpression reveals calcineurin as a key component in the transition from short term to long term Memory
    Cell, 1998
    Co-Authors: Isabelle M Mansuy, Eric R. Kandel, Mark Mayford, Betsy Jacob, Mary Elizabeth Bach
    Abstract:

    To investigate the roles phosphatases play in Hippocampal-Dependent Memory, we studied transgenic mice overexpressing a truncated form of calcineurin. These mice have normal short-term Memory but defective long-term Memory evident on both a spatial task and on a visual recognition task, providing genetic evidence for the role of the rodent hippocampus in spatial and nonspatial Memory. The defect in long-term Memory could be fully rescued by increasing the number of training trials, suggesting that the mice have the capacity for long-term Memory. We next analyzed mice overexpressing calcineurin in a regulated manner and found the Memory defect is reversible and not due to a developmental abnormality. Our behavioral results suggest that calcineurin has a role in the transition from short- to long-term Memory, which correlates with a novel intermediate phase of LTP.

  • impairment of spatial but not contextual Memory in camkii mutant mice with a selective loss of hippocampal ltp in the range of the θ frequency
    Cell, 1995
    Co-Authors: Mary Elizabeth Bach, Eric R. Kandel, Robert D Hawkins, Mona Osman, Mark Mayford
    Abstract:

    We assessed Hippocampal-Dependent Memory in mice with a Ca(2+)-independent form of CaMKII generated by the introduction of an aspartate at amino acid 286. The CaMKII-Asp-286 mice show normal LTP at high frequency stimulation, but in the 5-10 Hz range, they show a shift in the frequency-response curve favoring LTD. This range of frequencies is similar to the theta rhythm, which is associated with exploration in rodents. Using the Barnes maze to assess spatial Memory, we found the transgenic mice could not learn to navigate to a specific location using spatial cues. In contrast, one line of transgenic mice performed normally in contextual fear conditioning, a task that is also hippocampal dependent. This dissociation between spatial and contextual Memory suggests that even though both require the hippocampus, they may be mediated by different synaptic mechanisms.