NOVELTY INDUCED FACILITATION OF HIPPOCAMPAL LTP

本课题的目的是研究新奇感诱导的长时程增强易化现象。LTP是一种突触可塑性机制，可能是某些学习形式的基础。在内侧穿通路径投射到齿状回诱导的LTP诱导清醒、自由移动的动物在单次刺激会话后持续3-5天6/24/51。然而，如果在探索新环境的前5-20分钟期间诱导LTP，则LTP诱导的概率和LTP的幅度都增加。此外，在新环境中诱导的LTP在单次刺激会话后平均持续10天。这些影响与大脑温度和运动以及探索过程中发生的θ节律无关。重要的是，重复暴露于相同的新环境会逐渐减少LTP的促进作用。相比之下，在饲养笼中诱导的LTP在幅度和时间过程上与重复诱导一致。因此，似乎熟悉的环境降低了新奇促进效应。这些数据表明，与新奇感检测和/或与探索性行为相关的唤醒相关的过程促进了LTP的诱导和寿命。在这些研究中，我们将解决行为，药理学和解剖学方面的新奇诱导的促进。具体目标1中的研究将确定易化的时间进程，并评估在新环境中放置后易化的寿命。我们还将评估是否熟悉的基础上观察到的递减与重复暴露于相同的新环境，通过确定是否返回到一个熟悉的环境中的动物迅速逆转新奇诱导的促进作用，如果不同的新环境导致重新出现的LTP促进。在具体目标2中，将使用药理学方法来确定在探索和唤醒期间活跃的神经调节系统是否有助于LTP诱导和维持的新奇诱导的易化。我们将研究胆碱能，肾上腺素能和阿片类神经调节系统的贡献，这种促进作用，其中每一个是积极的探索。具体目标3的研究，我们将确定是否新的环境类似地改变LTP诱导和LTP维持在Schaffer-CA 1投射，连合-CA 3投射，和直接贯穿路径投射到海马CA 3区。这些研究将使我们能够确定新奇和神经调节系统对海马初级突触系统LTP诱导的影响，并解决神经调节剂和新奇检测在记忆储存过程中的作用，这可能与记忆障碍和海马信息处理的当前模型有关。

The goal of this project is to investigate the phenomenon of novelty- induced facilitation of long-term potentiation (LTP). LTP is a mechanism of synaptic plasticity that may underlie certain forms of learning. LTP induced in medial perforant path projections to the dentate gyrus induce din awake, freely-moving animals persists from 3-5 days following a single stimulation session 6/24/51. However, if LTP is induced during the first 5-20 minute period of exploration of a novel environment, then both the probability of LTP induction and the magnitude of LTP are increased Further, LTP induced in a novel environment persists for an average of 10 days following a single stimulation session. These effects are independent from both brain temperature and movement, as well as theta rhythm occurring during exploration. Importantly, repeated exposure to the same novel environment produces progressively less facilitation of LTP. By contrast, LTP induced in the home cage is consistent in magnitude and time course with repeated induction. Thus, it appears familiarity with the environment reduces the novelty facilitation effect. These data indicate that processes(s) associated with the detection of novelty and/or arousal associated with exploratory behaviors facilitate LTP induction and longevity. In these studies, we will address behavioral, pharmacological and anatomical aspects of novelty-induced facilitation. The studies in Specific Aim 1 will determine the time course of facilitation, and assess the longevity of facilitation following placement in a novel environment. We will also assess whether familiarity underlies the decrement observed with repeated exposures to the same novel environment by determining if returning the animal to a familiar environment rapidly reverses the effect of novelty-induced facilitation, and if distinct novel environments lead to re-emergence of LTP facilitation. In Specific Aim 2, pharmacological methods will be used to determine if neuromodulatory systems that are active during exploration and arousal contribute novelty-induced facilitation of LTP induction and maintenance. We will investigate the contribution of cholinergic, adrenergic and opiodergic neuromodulatory systems to this facilitation effect, each of which are active during exploration. The studies of Specific Aim 3, we will determine if novel environments similarly alter LTP induction and LTP maintenance in Schaffer-CA1 projections, commissural-CA3 proje3ctions, and direct perforant path projections to hippocampal area CA3. These studies will allow us to determine the effects of novelty and neuromodulatory systems on LTP induction in the primary synaptic systems of the hippocampus, and address the role of neuromodulators and novelty detection in processes of memory storage that may be relevant to both memory disorders and current models of hippocampal information processing.