Nicotine shifts the temporal activation of hippocampal protein kinase A and extracellular signal-regulated kinase 1/2 to enhance long-term, but not short-term, hippocampus-dependent memory

作者：Gould Thomas J^*; Wilkinson Derek S; Yildirim Emre; Poole Rachel L F; Leach Prescott T; Simmons Steven J

来源：Neurobiology of Learning and Memory, 2014, 109: 151-159.

DOI：10.1016/j.nlm.2014.01.009

• Learning
• Plasticity
• Protein synthesis
• Addiction
• Acetylcholine

Acute nicotine enhances hippocampus-dependent learning through nicotine binding to beta 2-containing nicotinic acetylcholine receptors (nAChRs), but it is unclear if nicotine is targeting processes involved in short-term memory (STM) leading to a strong long-term memory (LTM) or directly targeting LTM. In addition, the molecular mechanisms involved in the effects of nicotine on learning are unknown. Previous research indicates that protein kinase A (PICA), extracellular signal-regulated kinase 1/2 (ERK1/2), and protein synthesis are crucial for LTM. Therefore, the present study examined the effects of nicotine on STM and LTM and the involvement of PICA, ERK1/2, and protein synthesis in the nicotine-induced enhancement of hippocampus-dependent contextual learning in C57BL/6J mice. The protein synthesis inhibitor anisomycin impaired contextual conditioning assessed at 4 h but not 2 h post-training, delineating time points for STM (2 h) and LTM (4 h and beyond). Nicotine enhanced contextual conditioning at 4, 8, and 24 h but not 2 h post-training, indicating nicotine specifically enhances LTM but not STM. Furthermore, nicotine did not rescue deficits in contextual conditioning produced by anisomycin, suggesting that the nicotine enhancement of contextual conditioning occurs through a protein synthesis-dependent mechanism. In addition, inhibition of dorsal hippocampal PICA activity blocked the effect of acute nicotine on learning, and nicotine shifted the timing of learning-related PICA and ERK1/2 activity in the dorsal and ventral hippocampus. Thus, the present results suggest that nicotine specifically enhances LTM through altering the timing of PICA and ERK1/2 signaling in the hippocampus, and suggests that the timing of PICA and ERK1/2 activity could contribute to the strength of memories.

• 出版日期2014-3