Schimanski Lesley A, Nguyen Peter V
Department of Physiology, University of Alberta School of Medicine, Edmonton, Alberta T6G 2H7, Canada.
Hippocampus. 2005;15(4):502-17. doi: 10.1002/hipo.20075.
Inbred mouse strains have different genetic backgrounds that can result in impairments of synaptic plasticity and memory. They are valuable models for probing the mechanisms of memory impairments. We examined fear memory in several inbred strains, along with synaptic plasticity that may underlie fear memory. Long-term potentiation (LTP) is a form of activity-dependent synaptic plasticity that is a candidate cellular mechanism for some forms of learning and memory. Strains with impaired contextual or cued fear memory may have selective LTP deficits in different hippocampal subregions, or in the amygdala. We measured fear memory and its extinction in five inbred strains: C57BL/6NCrlBR (B6), A/J, BALB/cByJ (BALB), C57BL/10J (B10), and SM/J (SM). We also measured LTP in the basolateral amygdala and in the hippocampal Schaeffer collateral-commissural (SC) and medial perforant pathways (MPP). All strains exhibited intact contextual fear memory 24 h post-training, but cued fear memory was impaired in strains A/J, BALB, and SM. At 1 h post-training, both contextual and cued fear memory deficits were more widespread: all strains except for B6 and B10 showed impairments of both types of memory. Contextual fear extinction was impaired in BALB and SM. We found that amygdalar LTP was reduced in strains A/J and BALB, but SC LTP was intact in all strains (except for a selective multi-train LTP impairment in BALB). MPPLTP was similar in all five strains. Thus, reduced amygdalar LTP is correlated with impaired cued fear memory in strains A/J and BALB. Also, hippocampal SC LTP is more strongly correlated with 24-h (long-term) than with 1-h (short-term) contextual fear memory. In this first conjoint study of amygdala-dependent memory and amygdalar LTP in inbred mice, we identified specific hippocampal and amygdalar LTP deficits that correlate with fear memory impairments. These deficits should be considered when selecting inbred strains for genetic modification.
近交系小鼠品系具有不同的遗传背景，这可能导致突触可塑性和记忆受损。它们是探究记忆损伤机制的有价值模型。我们研究了几种近交系中的恐惧记忆，以及可能是恐惧记忆基础的突触可塑性。长时程增强（LTP）是一种依赖活动的突触可塑性形式，是某些形式学习和记忆的候选细胞机制。情境性或线索性恐惧记忆受损的品系可能在不同的海马亚区或杏仁核中存在选择性LTP缺陷。我们测量了五个近交系的恐惧记忆及其消退情况：C57BL/6NCrlBR（B6）、A/J、BALB/cByJ（BALB）、C57BL/10J（B10）和SM/J（SM）。我们还测量了基底外侧杏仁核、海马的谢弗侧支-连合通路（SC）和内侧穿通通路（MPP）中的LTP。所有品系在训练后24小时均表现出完整的情境性恐惧记忆，但A/J、BALB和SM品系的线索性恐惧记忆受损。在训练后1小时，情境性和线索性恐惧记忆缺陷更为普遍：除B6和B10外，所有品系都表现出两种类型记忆的损伤。BALB和SM品系的情境性恐惧消退受损。我们发现A/J和BALB品系的杏仁核LTP降低，但所有品系（除BALB中的选择性多训练LTP损伤外）的SC LTP均完整。所有五个品系的MPP LTP相似。因此，杏仁核LTP降低与A/J和BALB品系的线索性恐惧记忆受损相关。此外，海马SC LTP与24小时（长期）情境性恐惧记忆的相关性比与1小时（短期）情境性恐惧记忆的相关性更强。在这项对近交系小鼠中依赖杏仁核的记忆和杏仁核LTP的首次联合研究中，我们确定了与恐惧记忆损伤相关的特定海马和杏仁核LTP缺陷。在选择用于基因改造的近交系时应考虑这些缺陷。
