- Email: [email protected]
Dynamic regulation of fear memory after retrieval
Abstracts / Neuroscience Research 71S (2011) e6–e44
patients especially with depression after myocardial infarction and hypertrophy. Research fund: KAKENHI (22390109).
References Bhuiyan, M.S., Fukunaga, K., 2011. Targeting sigma-1 receptor signaling by endogenous ligands for cardioprotection. Expert Opin. Ther. Targets 15: 145–155. Narita, N., Hashimoto, K., et al., 1996. Eur. J. Pharmacol. 307, 117–119.
doi:10.1016/j.neures.2011.07.149
S4-B-1-1 retrieval Satoshi 1 2
Dynamic regulation of fear memory after
Kida 1,2
, Hotaka
Fukushima 1,2 ,
Yue
Zhang 1,2
Department of Bioscience, Tokyo University Agriculture, Tokyo, Japan CREST, JST
Memory retrieval initiates opposite processes; memory reconsolidation and extinction. It is thought that memory reconsolidation is a process to maintain or strengthen original memory, while memory extinction is a process to weaken original memory. We have tried to understand the dynamic nature of memory after retrieval using contextual fear conditioning test. However, contextual fear conditioning allows to induce reconsolidation by re-exposure to the CS without US (CS-no US) in the experimental conditions where extinction is also induced. Therefore, it is difficult to investigate mechanisms by which the fate of memory is determined after retrieval; retrieved memory is either reconsolidated or extinguished. In this study, we have tried to understand these mechanisms using light–dark inhibitory avoidance task. We found that this task allows to discriminate reconsolidation and extinction phases at the time point when mice enter into the dark box from the light box. Re-exposure to light box led to enhancement of fear memory, while the subsequent re-exposure to the dark for 10 min after mice enter from light box led to memory extinction. More interestingly, the re-exposure to the dark box for 1 min was sufficient to abolish the enhancement of fear memory following the re-exposure to only light box. We are now investigating mechanisms underlying the determination of memory fate after retrieval at the anatomical, cellular and molecular levels. Research Fund: CREST, JST, KAKENHI. doi:10.1016/j.neures.2011.07.150
S4-B-1-2 Non-associative place memory is precisely maintained during the reorganization process of neuronal substrates underlying remote memory formation Takashi Kitamura 1,2,3 , Kaoru Inokuchi 1,3 1 Department of Biochemistry, Graduate School of Medicine & Pharmaceutical Sciences, University of Toyama, Japan 2 The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Japan 3 JST, CREST, Kawaguchi, Japan
While location-specific firing pattern in a place is long-lastingly represented in hippocampal pyramidal cells after novel place exploration, it is not clear yet that the place memory is similarly maintained. Here our new protocol, non-associative place memory procedure in mice, revealed that the memory is quickly formed and precisely long-lastingly maintained like hippocampal representations. But, unexpectedly the remote memory might be supported by extra-hippocampal brain region. doi:10.1016/j.neures.2011.07.151
S4-B-1-3 Spatial learning: A sculptor of neo-networks Djoher Nora Abrous Inserm U862, Neurocentre Magendie, Université de Bordeaux, Bordeaux, France During embryonic development, neuronal activity sculpts neuronal networks. Indeed, after an initial overproduction of neurons and contacts, regressive events will stabilize a particular set of contacts among many, thereby sculpting the precise circuits that are crucial for a given function. We will show that similarly to this selective stabilization process, adult neuronal networks are sculpted during learning. Indeed, the adult dentate gyrus has the peculiarity to produce new neurones throughout the life of an individual. This region is crucially involved in memory and increasing evidence suggests that the addition of adult-born neurons contribute to memory processes. We will show that spatial learning regulates homeostatically the number of
e35
new neurons and shapes the dendritic arbor of the set of new neurons stabilized by learning. This “epigenetic” specification of neo-neonetworks are long lasting, depend upon the level of cognitive demand and NMDA receptors. Altogether, these results showed that in addition to remodelling pre-exiting networks, learning sculpts novel networks. In the search for the structural changes underlying long-term memory, these findings highlight that shaping neo-networks is important in forming spatial memories. Research fund: INSERM, University of Bordeaux 2, ANR. doi:10.1016/j.neures.2011.07.152
S4-B-1-4 Role of adult neurogenesis in the hippocampal circuit function Tatsuhiro Hisatsune Dept. Integrated Biosciences, University Tokyo, Chiba, Japan New neurons generate at the dentate gyrus of the hippocampal formation throughout life. Recent studies well indicate the essential role of new neurons in the cognitive function of the hippocampal circuit. Basically, new neurons receive inputs from entorhinal cortex via the perforant pathway and send mossy fiber axon toward CA3 pyramidal neurons. In addition, young new neurons receive cholinergic inputs as well as GABAergic inputs and give neural outputs toward hilar neurons, such as glutamatergic mossy cells or GABAergic local interneurons. New neuron-related hippocampal circuit should take part in the formation of memory engram, either at the CA3 area or the dentate gyrus area. To know the direct involvement of new neuron circuit in the hippocampal circuit function, we utilized optogenetics-fMRI (opto-fMRI) methods in the combination of gamma-ray irradiation, in which the dentate neurons of Thy1-ChR2 rat (gifted from Drs. Fukazawa and Yawo) are photo-activated in the scanner of 4.7 T MRI machine and the activation of CA3 neurons are evaluated by BOLD signal. Research fund: KAKENHI 22120505. doi:10.1016/j.neures.2011.07.153
S4-B-1-5 Pattern separation in the hippocampus: A role for adult neurogenesis and BDNF Tim Bussey Department of Experimental Psychology and MRC and Wellcome Trust Behavioural and Clinical Neurosciences Institute, University of Cambridge, Cambridge, UK To allow similar episodes to be distinguished in memory, the brain must form distinct representations of events. The computational process for making representations for similar input patterns more orthogonal to and distinct from each other – so that they are less easily confused in memory – has been referred to as “pattern separation”. Recent studies have suggested that the brain region crucial for this process is the dentate gyrus (DG) of the hippocampus. It is largely unknown, however, what mechanisms and molecules underlie pattern separation. In my talk I will describe recent published evidence that adult neurogenesis in the DG is particularly important for pattern separation. In addition I will introduce some new, unpublished data indicating that brain-derived neurotrophic factor (BDNF), a small dimeric secretory protein with an important role in excitatory transmission and plasticity, is also critical for this important mnemonic function. Research fund: BBSRC, U.K. doi:10.1016/j.neures.2011.07.154
S4-C-1-1 BDNF and mood disorders: New insights from neurobiology to applied physics Masami Kojima 1,2 1 2
Bio-interface Research Group, Health Research Inst. AIST, Ikeda, Japan CREST, JST, Kawaguchi, Japan
Volumetric decreases observed in the hippocampus and other forebrain regions in subsets of depressed patients have led to a hypothesis that depression may involve decreases in neurotrophic factors that control synaptic plasticity and neuronal morphology. Previous studies have extensively focused on a role for brain-derived neurotrophic factor (BDNF), which is abundantly expressed in adult brain structures. This ‘BDNF hypothesis’ is supported by large preclinical and clinical reports that show that some forms of stress reduce BDNF signaling, while chronic treatment with antidepressants increases this signaling. Similar responses have been observed in the post-mortem human brain with depression, as well as in the concentrations of serum BDNF. Here, I will provide our new findings BDNF to support and
patients especially with depression after myocardial infarction and hypertrophy. Research fund: KAKENHI (22390109).
References Bhuiyan, M.S., Fukunaga, K., 2011. Targeting sigma-1 receptor signaling by endogenous ligands for cardioprotection. Expert Opin. Ther. Targets 15: 145–155. Narita, N., Hashimoto, K., et al., 1996. Eur. J. Pharmacol. 307, 117–119.
doi:10.1016/j.neures.2011.07.149
S4-B-1-1 retrieval Satoshi 1 2
Dynamic regulation of fear memory after
Kida 1,2
, Hotaka
Fukushima 1,2 ,
Yue
Zhang 1,2
Department of Bioscience, Tokyo University Agriculture, Tokyo, Japan CREST, JST
Memory retrieval initiates opposite processes; memory reconsolidation and extinction. It is thought that memory reconsolidation is a process to maintain or strengthen original memory, while memory extinction is a process to weaken original memory. We have tried to understand the dynamic nature of memory after retrieval using contextual fear conditioning test. However, contextual fear conditioning allows to induce reconsolidation by re-exposure to the CS without US (CS-no US) in the experimental conditions where extinction is also induced. Therefore, it is difficult to investigate mechanisms by which the fate of memory is determined after retrieval; retrieved memory is either reconsolidated or extinguished. In this study, we have tried to understand these mechanisms using light–dark inhibitory avoidance task. We found that this task allows to discriminate reconsolidation and extinction phases at the time point when mice enter into the dark box from the light box. Re-exposure to light box led to enhancement of fear memory, while the subsequent re-exposure to the dark for 10 min after mice enter from light box led to memory extinction. More interestingly, the re-exposure to the dark box for 1 min was sufficient to abolish the enhancement of fear memory following the re-exposure to only light box. We are now investigating mechanisms underlying the determination of memory fate after retrieval at the anatomical, cellular and molecular levels. Research Fund: CREST, JST, KAKENHI. doi:10.1016/j.neures.2011.07.150
S4-B-1-2 Non-associative place memory is precisely maintained during the reorganization process of neuronal substrates underlying remote memory formation Takashi Kitamura 1,2,3 , Kaoru Inokuchi 1,3 1 Department of Biochemistry, Graduate School of Medicine & Pharmaceutical Sciences, University of Toyama, Japan 2 The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Japan 3 JST, CREST, Kawaguchi, Japan
While location-specific firing pattern in a place is long-lastingly represented in hippocampal pyramidal cells after novel place exploration, it is not clear yet that the place memory is similarly maintained. Here our new protocol, non-associative place memory procedure in mice, revealed that the memory is quickly formed and precisely long-lastingly maintained like hippocampal representations. But, unexpectedly the remote memory might be supported by extra-hippocampal brain region. doi:10.1016/j.neures.2011.07.151
S4-B-1-3 Spatial learning: A sculptor of neo-networks Djoher Nora Abrous Inserm U862, Neurocentre Magendie, Université de Bordeaux, Bordeaux, France During embryonic development, neuronal activity sculpts neuronal networks. Indeed, after an initial overproduction of neurons and contacts, regressive events will stabilize a particular set of contacts among many, thereby sculpting the precise circuits that are crucial for a given function. We will show that similarly to this selective stabilization process, adult neuronal networks are sculpted during learning. Indeed, the adult dentate gyrus has the peculiarity to produce new neurones throughout the life of an individual. This region is crucially involved in memory and increasing evidence suggests that the addition of adult-born neurons contribute to memory processes. We will show that spatial learning regulates homeostatically the number of
e35
new neurons and shapes the dendritic arbor of the set of new neurons stabilized by learning. This “epigenetic” specification of neo-neonetworks are long lasting, depend upon the level of cognitive demand and NMDA receptors. Altogether, these results showed that in addition to remodelling pre-exiting networks, learning sculpts novel networks. In the search for the structural changes underlying long-term memory, these findings highlight that shaping neo-networks is important in forming spatial memories. Research fund: INSERM, University of Bordeaux 2, ANR. doi:10.1016/j.neures.2011.07.152
S4-B-1-4 Role of adult neurogenesis in the hippocampal circuit function Tatsuhiro Hisatsune Dept. Integrated Biosciences, University Tokyo, Chiba, Japan New neurons generate at the dentate gyrus of the hippocampal formation throughout life. Recent studies well indicate the essential role of new neurons in the cognitive function of the hippocampal circuit. Basically, new neurons receive inputs from entorhinal cortex via the perforant pathway and send mossy fiber axon toward CA3 pyramidal neurons. In addition, young new neurons receive cholinergic inputs as well as GABAergic inputs and give neural outputs toward hilar neurons, such as glutamatergic mossy cells or GABAergic local interneurons. New neuron-related hippocampal circuit should take part in the formation of memory engram, either at the CA3 area or the dentate gyrus area. To know the direct involvement of new neuron circuit in the hippocampal circuit function, we utilized optogenetics-fMRI (opto-fMRI) methods in the combination of gamma-ray irradiation, in which the dentate neurons of Thy1-ChR2 rat (gifted from Drs. Fukazawa and Yawo) are photo-activated in the scanner of 4.7 T MRI machine and the activation of CA3 neurons are evaluated by BOLD signal. Research fund: KAKENHI 22120505. doi:10.1016/j.neures.2011.07.153
S4-B-1-5 Pattern separation in the hippocampus: A role for adult neurogenesis and BDNF Tim Bussey Department of Experimental Psychology and MRC and Wellcome Trust Behavioural and Clinical Neurosciences Institute, University of Cambridge, Cambridge, UK To allow similar episodes to be distinguished in memory, the brain must form distinct representations of events. The computational process for making representations for similar input patterns more orthogonal to and distinct from each other – so that they are less easily confused in memory – has been referred to as “pattern separation”. Recent studies have suggested that the brain region crucial for this process is the dentate gyrus (DG) of the hippocampus. It is largely unknown, however, what mechanisms and molecules underlie pattern separation. In my talk I will describe recent published evidence that adult neurogenesis in the DG is particularly important for pattern separation. In addition I will introduce some new, unpublished data indicating that brain-derived neurotrophic factor (BDNF), a small dimeric secretory protein with an important role in excitatory transmission and plasticity, is also critical for this important mnemonic function. Research fund: BBSRC, U.K. doi:10.1016/j.neures.2011.07.154
S4-C-1-1 BDNF and mood disorders: New insights from neurobiology to applied physics Masami Kojima 1,2 1 2
Bio-interface Research Group, Health Research Inst. AIST, Ikeda, Japan CREST, JST, Kawaguchi, Japan
Volumetric decreases observed in the hippocampus and other forebrain regions in subsets of depressed patients have led to a hypothesis that depression may involve decreases in neurotrophic factors that control synaptic plasticity and neuronal morphology. Previous studies have extensively focused on a role for brain-derived neurotrophic factor (BDNF), which is abundantly expressed in adult brain structures. This ‘BDNF hypothesis’ is supported by large preclinical and clinical reports that show that some forms of stress reduce BDNF signaling, while chronic treatment with antidepressants increases this signaling. Similar responses have been observed in the post-mortem human brain with depression, as well as in the concentrations of serum BDNF. Here, I will provide our new findings BDNF to support and