| 研究課題/領域番号 |
18K03168
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| 研究機関 | 筑波大学 |
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研究代表者 |
Pavlides C 筑波大学, 人間系, 研究員 (50712808)
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| 研究期間 (年度) |
2018-04-01 – 2023-03-31
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| キーワード | hippocampus / memory / immediate early genes / Zif268 / functional organization / sleep / spatial navigation / place cells |
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| 研究実績の概要 |
The proposed studies were designed to determine possible neuronal functional organization in the hippocampus for the encoding of different types of memories, including, spatial, sequential and fear memory, through the use of the activity dependent immediate early gene (IEG) Zif268. We found, counter to common belief, that pyramidal cells in the CA1/CA3 hippocampal fields are arranged in clusters of a few (3-4) active cells that spanned the extent of the dorsal region. A second objective was to determine the role that sleep may play in the consolidation of memory and the stabilization of the observed clusters. We found that indeed sleep succeeding conditioning enhanced long-term fear memory as well as showing more, closely packed neuronal clusters in the CA1 field. These previous studies provided evidence of a cluster organization, however, the mechanisms involved in the formation of clusters are not known. In a second set of experiments we are using optogenetic stimulation to inhibit/excite different subregions of the entorhinal cortex (EC) to first determine the role they may play in spatial/object-fear memory. Further, we have been analyzing possible topographic neuronal distribution in the hippocampal CA1 to determine whether the inputs from EC provide the drive for the clusters to form. We have, thus far, gathered sufficient evidence to show that inhibition of medial and lateral EC suppress spatial/object-fear memory.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
The first two studies have been completed and manuscripts are in preparation/have been submitted for publication. In the first optogenetic study we have completed the behavioral testing as well as a substantial part of the neuroanatomical investigation. However, further analysis will be required for the reconstruction of the neuronal distribution both in the EC and the hippocampus. For the second study, in which we optogenetically excite EC afferents to determine hippocampal neuronal organization, we still have to increase the number of animals used. We anticipate that processing of these brains and final analysis of the immunohistochemistry should be completed within the next few months following which one possibly two manuscripts will be prepared for publication.
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| 今後の研究の推進方策 |
Completion of the studies will require further immunohistochemistry/image processing/analysis of the anatomical data for the first study while for the second study, we have to increase the number of animals as well as process the neuroanatomical data. That is a very time and labor intensive task. As stated above, two experiments have been ongoing. The first was to suppress neuronal activity in either the MEC or LEC using optogenetic stimulation and observe behavioral effects in a spatial/object fear-memory task. The behavioral data has now been completed. Further, the majority of the brains have been processed for immunohistochemical/image analysis of IEG expression, although a few brains still remain to be processed. Further, some of the image analysis will have to be completed along with data/statistical analysis. For the second study, to determine effects of MEC/LEC optogenetic stimulation on hippocampal neuronal organization, we have completed a number of experiments, however, will still have to increase the number of animals. This too is very time consuming, including stereotaxic surgery for bilateral viral infections, optogenetic probe implantation, immunohistochemistry/image analysis, etc. It is estimated that this part of the study will require an additional few months to complete.
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| 次年度使用額が生じた理由 |
The carry over amount will be used mainly for IHC/image analysis. Immunohistochemistry supplies, including antibodies, reagents, etc. will have to be purchased. We are also anticipating a number of publications which should be completed during next year's budget period which will require substantial publication costs.
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