The long term objective of this proposal is to study synaptic reorganization of the hipocampus, and the potential of neural grafts and neurotrophic factors to enhance post lesion recovery and diminish aberrant regeneration. This is a well-written proposal with clearly stated goals and straightforward hypotheses regarding the consequences of aberrant connections that result from axonal growth. The Preliminary Data section is very well organized with the first several sections describing the degenerative events that result from a kainic acid injection into CA3, and the kinds of material that this team will be working with. This reviewer would have liked to have seen one of the quantitative analyses for parvalbumin, calbindin, calretinin or GAD actually carried through to fruition. The BrdU technique is impressive and will be extremely helpful in these studies, and the neurosphere experiments are also quite innovative and may represent a powerful approach. Also, the quantitative study outlined in Figures 7 and 8 on reconstruction of a transplant, and graft cell survival and disbursement is a good example of how they will use the NeuroLucida software. This reviewer would strongly recommend that they take these analyses to the next step beyond the distribution data in Figure 7, and generate actual cell counts with a sterological design. Such software is available from NeuroLucida, and could therefore easily be added on to their present approach, and this analysis of the viability of a graft is a perfect opportunity to use sterological methods to their best advantage. They would then be able to get precise, accurate counts of the total number of cells that survive in a transplant as well as their distribution and disbursement. This same suggestion goes for the rest of their cell count analysis as well, such as the analyses of interneurons.
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