BARDGETT POST-DOC/TECHNICIAN SUPPORT

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 拟议研究的目标是开发和使用中度兴奋性海马损伤模型，以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，兴奋性毒性损伤背海马产生持久的空间工作记忆的赤字。我们还表明，在初步研究中，组胺H3受体拮抗剂减轻损伤引起的空间工作记忆的缺陷。我们目前资助的R15研究的具体目标是回答以下问题：1）H3拮抗剂能否减轻成年发作海马损伤大鼠的空间工作记忆缺陷，2）将H3拮抗剂直接输注到前额皮质能否改善成年发作海马损伤大鼠的记忆，& 3）H3拮抗剂能否减轻空间工作记忆、前脉冲抑制、和自发活动的关系？对于此应用程序，我们要求INBRE补充支持研究助理谁可以推进我们的R15研究的目标和监督本科生研究。从2009年5月至今，我们评估了H3拮抗剂对空间记忆缺陷和其他行为异常的影响，这些异常是由阻断NMDA受体的药物引起的。这些研究主要由我们的研究助理Molly Griffith和实验室的几名本科生进行，表明H3拮抗剂加剧了NMDA拮抗剂对运动活动的影响，但也减轻了此类药物产生的空间记忆缺陷。我们于2009年6月提交了R15以继续这些研究，并获得了37分的优先级。我们将在2010年2月修改并重新提交此申请。拥有INBRE对我们的研究助理的支持极大地促进了我们的R15研究的步伐，并导致了两篇发表的论文，对获奖的本科研究的支持，以及R15续期申请，获得了有利的（虽然不可资助）分数。

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.