2015 Fiscal Year Research-status Report
Neural network organization of the spatial map
| Project/Area Number |
15K13157
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| Research Institution | University of Tsukuba |
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Principal Investigator |
Pavlides C 筑波大学, 人間系, 教授 (50712808)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Keywords | hippocampus / memory / place cells / episodic memory / immediate early genes |
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| Outline of Annual Research Achievements |
Using the immediate early gene Zif268 as a marker of neuronal activity, we have previously shown that in animals engaged in a spatial task, there is a cluster-type functional neuronal organization in the hippocampus, contrary to the widely held view of a random organization. During the first funding period, we also observed a similar organization in animals engaged in a sequential order odor discrimination task (Cho, et al., in preparation). We hypothesized that a cluster-type organization may constitute a basic functional unit of the hippocampus. During the past funding period, we undertook a set of experiments to test whether a cluster-type organization also occurs in a simple olfactory discrimination task, which is known to be hippocampus dependent. Similar to what we found with the sequential order odor discrimination task, there were both a lower number of zif268 immunoreactive cells as well as cell clusters in the CA1 hippocampal field in the simple olfactory discrimination task animals. In the CA3, there were a higher number of both cells and cell clusters in the experimental as apposed to the control animals in both the sequential and simple odor discrimination tasks, even though the overall number of clusters and cells were higher in the sequential order discrimination task. These results demonstrate that for each of the hippocampal dependent tasks described above a similar type of neuronal organization exists, further strengthening our original hypothesis. These results will be very constructive in pursuing the experiments planned for the next funding period.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
Initially we had used a delayed non-match to sample task to test functional hippocampal organization, however, we failed to observe significant differences between experimental and control animals. This could be due to the appropriateness of IEG methods to detect complex changes in neuronal activity. The positive results from the odor discrimination experiments gives us another memory task that can be used to test our hypothesis and thus will serve us well in future planed experiments. Besides using Zif268 to detect neuronal activation, it would be essential for us to use a different immediate gene to both confirm the results and their validity but to also be able to use two different genes to perform double labelling in animals performing two different tasks. This will be necessary to determine whether the same or different sets` of neurons encode for different types of memory. During the past funding period we have been performing preliminary immunohistochemical analysis using the IEG's Arc and Homer 1a. Although initially we faced a lot of difficulty getting reliable staining with these antibodies, we are currently getting better results and should be able to use these in ongoing experiments.
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| Strategy for Future Research Activity |
We are currently planning two sets of experiments - first we will attempt to determine whether the same or separate sets of hippocampal neurons are activated for different types of tasks (i.e., different types of memories) or whether the same cells may be involved in all. Using the catFISH double labeling method for different IEG's, we will train rats in a spatial task as well as a declarative memory task, following which IEG imaging will be performed. Given previous unit recording findings, we expect that some of the same cells could be involved in networks encoding different memories, although this will have to be verified experimentally. In a second set of experiments, we will test the validity of the cell clusters by differentially suppressing the various inputs into the hippocampus that relay specific spatial or non-spatial information and determining how the clusters may be affected. If indeed the clusters we have observed encode for different types of information then lesions or temporary inactivation of the afferents should disrupt them. Furthermore, if we observe that different sets of clusters encode for different types of information, than our targeted lesions should affect the clusters differentially - e.g., medial entorhinal cortex lesions should disrupt spatial clusters while lateral entorhinal lesions should disrupt declarative memory clusters. Positive results in these experiments should solidify the hypothesis of cluster-type organization in the hippocampus.
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| Causes of Carryover |
The studies involve doing immunohistochemistry which would require a significant budget for IEG antibodies, processing chemicals, etc. We have been testing various IEG antibodies (e.g., Arc, Homer 1a) that can be used as indicators of neuronal activity. However, the reactivity of these has not been optimal. Currently we are getting better results. Once these are optimized, we will be performing many of the experiments which will require the expenditure of significant funds. The immunohistochemistry will also require a considerable amount of effort which may require the hiring of a part time technician. Finally, the studies are already producing significant data which will require publication fees.
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| Expenditure Plan for Carryover Budget |
A significant part of the budget will be spent on the purchase of antibodies, chemicals and other supplies for immunohistochemistry. The immunohistochemistry will also involve a considerable amount of effort which may require the hiring of a part time technician. We have also established a collaboration with a person experienced in catFISH double labelling immunohistochemistry who will assist with the proposed studies. This will require travel funds. Finally some of the funds will be used for publication fees.
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Research Products
(3 results)
