BARDGETT POST-DOC/TECHNICIAN SUPPORT

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 这项拟议的研究的目标是开发和使用适度的兴奋性毒性海马区损伤模型来评估特定候选化合物的认知增强能力。我们的初步数据表明，对背侧海马区的兴奋毒性损伤会导致空间工作记忆的持久缺陷。我们还在初步研究中表明，组胺H3受体拮抗剂可以缓解损伤诱导的空间工作记忆缺陷。我们目前资助的R15研究的具体目的是回答以下问题：1)H3拮抗剂能否缓解成年性海马损伤大鼠的空间工作记忆缺陷；2)H3拮抗剂直接注入前额叶皮质能否改善成年性海马损伤大鼠的记忆；3)H3拮抗剂能否缓解新生发作性海马损伤大鼠的空间工作记忆、脉冲前抑制和运动活动的变化？对于这一申请，我们请求INBRE为一名研究助理提供补充支持，该助理可以推进我们R15研究的目标，并监督本科生的研究。从2009年5月到现在，我们评估了H3拮抗剂对空间记忆缺陷和其他由阻断NMDA受体的药物所产生的行为异常的影响。这些研究主要由我们的研究助理莫莉·格里菲斯和实验室的几名本科生进行，研究表明，H3拮抗剂加剧了NMDA拮抗剂对运动活动的影响，但也缓解了此类药物造成的空间记忆缺陷。我们在2009年6月提交了R15来继续这些研究，它的优先级分数为37。我们将在2010年2月修改并重新提交此申请。INBRE对我们的研究助理的支持极大地加快了我们R15研究的步伐，并导致了两篇发表的论文，对获奖的本科生研究的支持，以及获得有利(尽管无法资助)分数的R15续签申请。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The goal of the proposed research is to develop and use models of modest excitotoxic hippocampal injury to assess the cognitive enhancing ability of specific candidate compounds. Our preliminary data demonstrate that excitotoxic injury to the dorsal hippocampus produces enduring deficits in spatial working memory. We have also shown in preliminary studies that antagonists at histamine H3 receptors alleviate injury-induced deficits in spatial working memory. The specific aims of our currently-funded R15 research have been to answer the following questions: 1) Can H3 antagonists alleviate spatial working memory deficits in rats with adult-onset hippocampal injury, 2) Can direct infusion of H3 antagonists into the prefrontal cortex improve memory in rats with adult-onset hippocampal injury, & 3) Can H3 antagonists alleviate changes in spatial working memory, prepulse inhibition, and locomotor activity in rats with neonatal-onset hippocampal injury? For this application, we requested INBRE supplemental support for a research associate who can advance the aims of our R15 research and supervise undergraduate research. Between May 2009 and the present, we have assessed the effects of H3 antagonists on spatial memory deficits and other behavioral anomalies produced by drugs that block NMDA receptors. These studies, mainly performed by Molly Griffith, our research associate, and several undergraduates in the lab, have shown that H3 antagonists exacerbate the effects of NMDA antagonists on locomotor activity, but also alleviate the spatial memory deficits produced by such drugs. We submitted an R15 to continue these studies in June 2009 and it received a priority score of 37. We will revise and resubmit this application in February 2010. Having INBRE support for our research associate has greatly facilitated the pace of our R15 research and resulted in two published papers, support for award-winning undergraduate research, and an R15 renewal application that received a favorable (although unfundable) score.