シンポジウム
29 記憶痕跡細胞の機能動態と多能性
29 Dynamics and multipotency of memory engram cells
座長：北村 貴司（University of Texas Southwestern Medical Center）・Vetere Gisella（パリ市立工業物理化学高等専門大学） |
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| 2022年7月2日 16:15～16:33 沖縄コンベンションセンター 会議場B1 第3会場
3S03e-01
The role of microglia in extinction of fear engrams
*PAUL FRANKLAND(1,2)
1. Hospital for Sick Children, 2. University of Toronto
Keyword: memory, engram , microglia, extinction
Microglia are the brain’s resident immune cells. Classical work has established that microglia can ‘sense’ neural activity, and shape brain circuits by eliminating weaker synaptic connections (i.e., pruning) that are tagged with complement proteins (Schafer et al., 2012). To date, this form of microglia-dependent pruning has been largely studied either in the developing brain or in the diseased brain (including Alzheimer’s disease) (Salter and Stevens, 2017). In contrast, here we ask whether microglia shape circuits in an experience-dependent manner in the healthy, adult brain. Data from two preliminary experiments support a role for microglia in regulating fear memory engrams. In the first experiment, we trained mice in a fear conditioning task where a context was paired with a mildly-aversive footshock. Subsequent extinction training, in which mice were exposed to the context without footshock, led to a reduction in conditioned fear in control mice. However, in mice in which we chemogenetically inhibited microglia, extinction was slowed, suggesting that microglia play an active role in extinction learning. Consistent with this, in a second experiment, we found that extinction learning recruited microglia specifically to ‘fear engram neurons’—the neurons that store the fear memory (Josselyn and Tonegawa, 2020). In this experiment, we used engram labeling approaches to tag neuronal ensembles in the hippocampus that were active during initial fear conditioning. We found that subsequent extinction training recruited microglia to engram cells. Compared to controls, microglia were found in close proximity to engram neurons in extinguished mice, forming apparent soma-soma contacts (Cserép et al., 2019). This microglia-engram neuron interaction following extinction learning is remarkable. Earlier work suggests that microglia can shape circuits in two ways. First, microglia may directly suppress neuronal activity, potentially via adenosine signaling (e.g., A1R receptors on neurons) (Badimon et al., 2020). Second, microglia may eliminate weakened synapses in a complement-dependent manner (Wilton et al., 2019). Accordingly, we hypothesize that microglial-dependent regulation of extinction is a two-step process. Following activity-dependent recruitment of microglia to engram cells, microglia first suppress and then remodel engram neurons. Using this working model as our framework, our studies are currently addressing the following questions: 1) Does modulation of microglia activity bidirectionally regulate extinction? 2) Does extinction training recruit microglia to engram neurons? 3) Does blocking microglia-engram interactions prevent extinction? | | 2022年7月2日 16:38～16:56 沖縄コンベンションセンター 会議場B1 第3会場
3S03e-02
Taste Salience Representation in the Insula
*Kobi rosenblum Rosenblum(1)
1. University of Haifa, Haifa, Israel
Keyword: Insula, Novel, Valance, Taste
Avoiding potentially harmful, and consuming safe food is crucial for the survival of living organisms. In addition to genetic and developmental programming, an animal can update and change what it likes or want to avoid during its life time. Taste experiences can represent novelty, avoidance and/or aversiveness in a certain strength and with different combinations. These three parameters are crucial to define the currently perceived taste salience for memory retrieval. At the same time, the availability of a given taste to serve as CS in conditioned taste aversion (CTA) is dependent on its salience. We use electrophysiology, imaging and genetic tools together with behavior to identify how engram or cellular activity represents taste updating salience in the IC. We found that taste salience information is encoded in the insular cortex (IC). Activity in anterior insula (aIC) layer IV-VI pyramidal neurons projecting to the basolateral amygdala (BLA) is correlative and necessary for aversive learning and retrieval, as well as the expression of neophobia towards novel tastants, but not learning taste familiarity. Interestingly, activity of Parvalbumin (PV) interneurons inhibiting IC layer IV-VI pyramidal neurons projecting to the BLA is also correlative and necessary for taste valance updating. At the same time activity in layer IV-VI pyramidal neurons projecting to the medial prefrontal cortex (mPFC) are correlative and necessary for learning taste familiarity and its expression. In order to better dissociate between cellular mechanisms underlying taste saliency encoding and updating we are looking currently into within IC circuit/s. | | 2022年7月2日 17:01～17:19 沖縄コンベンションセンター 会議場B1 第3会場
3S03e-03
Memory acquisition and consolidation in the neuronal network
*Gisella Vetere(1)
1. ESPCI Paris, France
Keyword: memory consolidation, spatial representation, artificial memory
How the brain processes information from the world outside us to save it in the neural network? Can we implant false memories bypassing the external experience via artificial manipulation of known neuronal pattern? Here I will show that, by simply knowing the identity of the cells responsible for encoding a specific external stimulus, it is possible to implant fully artificial memories in mice. To form a long-lasting memory trace, the brain undergoes a substantial rearrangement at both synaptic and systems level to support the stabilization and future recall of the experienced event. What are the regions involved in this stabilization process? I will explore a graph theory analysis of memory networks to show that this approach opens new doors in the discovery of brain regions and pathways involved in cognitive functions. While spatial information is processed by the coordinated activity of a spatial representation network, I will present data showing how these brain regions support memory consolidation by changing their activity over time. Finally, I will present the research interests of the C4 (Cerebral Codes and Circuits Connectivity) team that I am leading at the ESPCI in Paris: we are studying how neuronal codes used to process spatial information are modified during memory stabilization. To this aim, we take advantage of cutting-edge techniques including the use of miniaturized microscopes to detect calcium activity in deep brain regions in freely moving mice and optogenetics to manipulate target neuronal circuits and causally link their role to learning and memory processes. | | 2022年7月2日 17:24～17:42 沖縄コンベンションセンター 会議場B1 第3会場
3S03e-04
経験依存的な恐怖記憶エングラムの制御
Experience-dependent regulation of fear memory engram
*喜田 聡(1)
1. 東京大学
*Satoshi Kida(1)
1. The University of Tokyo
Keyword: fear memory, memory engram, reconsolidation, extinction
Memory retrieval is not a passive process. Brief fear memory retrieval triggers fear responses followed by memory reconsolidation, whereas long-time or repeated retrieval extinguishes fear memory. The memory circuits that contribute to fear and extinction have been identified, respectively. However, the discrimination and interaction of fear and extinction neurons have not well examined. We have identified and characterized “fear” and “extinction” neuron using contextual fear conditioning and inhibitory avoidance tasks. We found that c-fos positive neurons increased in the mPFC, hippocampus and amygdala when fear memories were reconsolidated, while these neurons increased in the mPFC and amygdala when the memories were extinguished (Suzuki et al., 2004; Mamiya et al., 2009; Fukushima et al., 2014, 2021). We then suggested that the amygdala shows distinct populations of “fear neurons” and “extinction neurons”, whereas the mPFC exhibits a single neuronal population of them. We are currently trying to understand the functional role of these neuron populations in terms of memory engrams. | | 2022年7月2日 17:47～18:05 沖縄コンベンションセンター 会議場B1 第3会場
3S03e-05
Experience-dependent observational fear in hippocampal-amygdala memory engram networks
*Takashi Kitamura(1)
1. University of Texas Southwestern Medical Center
Keyword: memory engram cells, Empathy, hippocampus, fear
The empathic ability to vicariously experience the other’s fearful situation, a process called observational fear (OF), is critical to survive in nature and function in society. OF can be facilitated by both prior similar fear experience in the observer and social familiarity with the demonstrator. However, the neural circuit mechanisms of experience-dependent OF (Exp OF) remain unknown. In this study, we investigated how ACC, BLA, dHPC and vHPC activity and the relationship across these brain regions contributes to Exp OF and Naive OF. We demonstrate that dorsoventral HPC to BLA pathways, without ACC, are crucial for Exp OF, while the ACC to BLA pathway is essential for Naive OF. Second, to understand the neural mechanisms about how the HPC-BLA networks mediate Exp OF, we addressed the role of memory engram cells in dHPC and BLA that encode prior similar own fear experience on Exp OF. We found that fear memory engram cells in BLA are reactivated during and are necessary for Exp OF. Dorsal HPC neurons generate fear memory engram cells in BLA during prior own fear experience, while ventral HPC neurons respond to the familiar demonstrator’s fearful situation, which reactivate fear memory engram cells in BLA to elicit Exp OF. Finally, in vivo calcium imaging revealed that the fear memory engram cells in BLA are activated during both own and the familiar demonstrator’s aversive moment. Therefore, we propose that memory engram circuits in the HPC-BLA govern the integration of perception-action coupling as a principle of Exp OF. | | | |
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