Cytokines and Memory Consolidation

描述（由申请人提供）：拟议的研究将探索 免疫系统和学习/记忆过程之间的相互作用， 检测白细胞介素1 β1）作用部位，2）作用源，3）机制 介导海马依赖性情境恐惧障碍的作用。到 确定IL-1 β是否作用于背侧海马， 记忆障碍，将在接受（a）的大鼠中测试背景恐惧， LPS（外周）或（B）IL-1 β（中枢）注射，而内源性背侧 海马IL-1 β被IL-1受体拮抗剂抑制 （IL-1ra）。为了确定脑源性IL-1 β的来源是否是 神经元和/或神经胶质，（a）单标记和（B）双标记免疫组织化学 将进行研究以检测海马中的细胞类型和细胞含量 在外周注射LPS后。为了探索IL-1 β是否会损害 通过改变背侧海马谷氨酸释放的背景恐惧，在体内 将进行微透析研究以测量（a）未刺激和（B） 外周注射LPS后KCl刺激谷氨酸释放。如果 LPS诱导谷氨酸释放的改变，IL-1 ra将被注入到 取样区域以确定这种改变是否是特异性介导的 IL-1 β这些研究将回答一些重要的问题， 以及促炎性细胞因子如何影响 记忆过程

DESCRIPTION (provided by applicant): The proposed research will explore interactions between the immune system and learning/memory processes by examining IL-1 beta?s 1) site of action, 2) source of action, and 3) mechanisms of action that mediate hippocampal dependent contextual fear impairments. To determine whether IL-1beta is acting at the dorsal hippocampus to produce memory impairments, contextual fear will be tested in rats which receive an (a) LPS (peripheral) or (b) IL-1 beta (central) injection while endogenous dorsal hippocampal IL-1 beta is being inhibited with IL-I receptor antagonist (IL-1ra). To determine whether the source of brain-derived IL-l beta is neuronal and/or glial, (a) single- and (b) double-label immunohistochemical studies will be conducted to detect cell type and cell content in hippocampus following a peripheral injection of LPS. To explore whether IL- l beta impairs contextual fear by altering dorsal hippocampal glutamate release, in vivo microdialysis studies will be conducted to measure (a) unstimulated and (b) KCl-stimulated glutamate release following a peripheral injection of LPS. If LPS induces alterations in glutamate release, IL-1ra will be infused into the sampling region to determine whether such alterations are mediated specifically by IL-1 beta. These studies will answer some important questions about where and how pro-inflammatory cytokines may act to impair hippocampal-dependent memory processes.