Action and function of the neuropeptide gastrin-releasing peptide in stress and memory formation

本提案旨在测试神经肽在恐惧记忆中的功能。大脑中复杂的神经网络允许对环境线索和信息处理做出适当的反应。不同的生理和情绪状态，如压力和快乐，会对神经网络的功能产生强烈的影响，从而影响感官线索的处理和记忆。这些状态依赖性变化背后的一个主要过程是神经调节。神经调节剂是一种通常由神经元释放的小分子和多肽，可以同时影响数百个神经元的代谢和转录状态。众所周知的神经调节剂是多巴胺、血清素和乙酰胆碱，它们分别对动机、快乐和注意力的调节和影响至关重要。另一种鲜为人知的神经调节剂是胃泌素释放肽GRP。GRP在受到压力刺激时从神经元中释放出来，以前的研究表明它在调节恐惧记忆中起作用。然而，关于GRP的研究只关注少数大脑区域和很少的行为影响。我们发现GRP及其受体在皮质区，即处理感觉输入、运动输出和高阶认知所需的大脑区域中有一个有趣的表达模式。这种表达模式表明GRP在这些大脑区域的记忆形成中起作用。我们的目的是阐明GRP对皮层神经元网络的影响及其在恐惧记忆调节中的功能。因此，我们研究可能在创伤后应激障碍的发展中发挥重要作用的信号通路。

This proposal is designed to test the function of neuropeptides in fear memory.Intricate neuronal networks in the brain allow proper reactions to environmental cues and processing of information. Different physiological and emotional states like stress and happiness can have strong impact onto functioning of neuronal networks and thus onto processing and memorization of sensory cues. One major process that underlies these state-dependent changes is neuromodulation. Neuromodulators are small molecules and peptides that are usually released from neurons and can influence metabolic and transcriptional states of hundreds of neurons simultaneously. Well-known neuromodulators are dopamine, serotonin and acetylcholine that are essential in the modulation and effects of motivation, happiness and attention respectively. One less well-known neuromodulator is the neuropeptide gastrin-releasing peptide, GRP. GRP is released from neurons upon stressful stimuli and previous studies suggested a role in the modulation of fear memories. Studies on GRP are however anecdotal focusing only on few brain areas and few behavioral effects. We found an interesting expression pattern of GRP and its receptor in cortical areas, brain areas that are required for processing of sensory inputs, motor outputs and higher order cognition. The expression pattern suggests a role for GRP in memory formation in these brain areas. We aim to elucidate the effects of GRP on cortical neuronal networks and its function in the modulation of fear memories. We thus investigate signaling pathways that might play an important role in the development of posttraumatic stress disorders.