Award Lecture
受賞講演 |
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| 7月25日（木）15:40～16:40 第1会場（朱鷺メッセ 4F 国際会議室）
1AL01e
Innate immune mechanisms of synapse remodeling during brain development and learning
Anna Victoria Molofsky（Molofsky Anna Victoria）
University of California San Francisco
Neuronal synapse formation and remodeling is essential to central nervous system (CNS) development and adult learning. As such, alterations in synapse development and function is a central feature of neuropsychiatric diseases including autism, epilepsy, and schizophrenia. Innate immune signals regulate tissue remodeling in the periphery, but how this impacts CNS synapses is largely unknown. We found that the IL-1 family cytokine Interleukin-33 (IL-33) is physiologically required to promote synapse remodeling and maintain neural circuit function in the developing brain. We found that IL-33 is primarily expressed by developing astrocytes, the structural glia of the brain. Astrocyte-derived IL-33 signals primarily to microglia under physiologic conditions to promote microglial synapse engulfment. This astrocyte-microglial signaling pathway is required for normal circuit function in the thalamus, a brain region important for synchronizing neural activity. In ongoing work, we have identified a unique subpopulation of IL-33 expressing neurons in the adult hippocampus, a brain region essential for learning and new memory formation. Neuronal expression of IL-33 is experience dependent, and conditional deletion of IL-33 from neurons or its receptor in microglia leads to both structural and functional deficits in hippocampal neurons and impaired hippocampal-dependent behaviors. These data indicate physiologic and homeostatic roles for IL-33 signaling in brain development and learning, raising the question of how this delicate balance may be altered in the context of type 2 immune challenges such as brain injury. | | 7月25日（木）16:50～17:50 第1会場（朱鷺メッセ 4F 国際会議室）
2AL01a
The circuits and physiology of hippocampal memory
Thomas J. Mchugh（Mchugh Thomas J.）
Lab for Circuit and Behavioral Physiology RIKEN Center for Brain Science
The hippocampus is one of the most well characterized and intensely studied regions of the mammalian brain. In rodents, its well defined anatomy, in vitro and in vivo physiology and role in spatial and contextual behavior make it an ideal model system to test hypotheses linking memory and neuronal information representations. My laboratory tackles these questions via a combination of in vivo recording and genetic tools. Today I will begin by highlight our use of circuit genetics to manipulate plasticity or transmission in individual hippocampal subfields (CA1/2/3/DG) to understand their unique contributions to specific mnemonic & physiological processes. I will then discuss more recent work on physiological signatures of encoding and recall which allow the identification of subsets of neurons involved in a memory trace. Finally, I will describe modulatory projections that can signal novelty to the hippocampal circuit and impact the way information in processed. Taken together, these findings suggest that while information flow in the hippocampus is often described as progressing from the entorhinal cortex (EC) sequentially along the tri-synaptic DG/CA3/CA1 axis, in fact, task and cognitive demands lead to a more complex regulation of multiple parallel circuits. | | 7月26日（金）15:50～16:50 第1会場（朱鷺メッセ 4F 国際会議室）
1AL01a
海馬長期増強現象の分子機構
Yasunori Hayashi（林 康紀）
京都大院医システム神経薬理
A transient modulation of synaptic input intensity causes a long-term change in the efficacy of subsequent synaptic transmission, phenomena collectively called synaptic plasticity. One of prototypical example is long-term potentiation (LTP) observed in hippocampus. A number of studies supports the idea that LTP is a cellular counter part of learning and memory. I have been interested in the molecular mechanism of hippocampal LTP. To elucidate this, I take a combinatorial approach of electrophysiology, imaging, and molecular biology. LTP processes can be largely divided into three phases; induction, expression, and maintenance. During induction process, a transient influx of Ca2+ through NMDA-type glutamate receptor (NMDAR) triggers a cascade of biochemical signaling, which eventually leads to an enhancement of AMPA-type glutamate receptor (AMPAR) transmission. I focus on my research how the AMPAR transmission specifically increases in the potentiated synapse and how it is maintained. I hypothesized that trafficking of AMPAR to the potentiated synapse explains expression of LTP. To this end, I used both imaging and electrophysiological approach to demonstrate this is the case. However, the activity-dependent synaptic trafficking is not limited to AMPAR. I found number of postsynaptic proteins traffic into the synapse at velocity and order specific to each protein. Among them, I found the actin and actin biding proteins are the first proteins to be trafficked. Consistently, Förster resonance energy transfer (FRET)-mediated measurement of actin polymerization status shows that actin is rapidly and persistently polymerized within the dendritic spine, which could serve as a binding site for number of synaptic proteins directly and indirectly. Then I went on to reveal the mechanism by which a transient Ca2+-signal is converted into persistent signaling that support actin polymerization. I found a positive a protein complex formed between Rac guanine-nucleotide exchange factor (RacGEF) Tiam1 and Ca2+/calmodulin-dependent protein kinase II (CaMKII) consists a self-activating loop that converts a transient Ca2+-signaling into persistent biochemical to support actin polymerization, which in turn maintain the potentiated synaptic transmission.
COI: Partly supported by Fujitsu Laboratories and Dwango. | | | |
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