Cai Denise J, Aharoni Daniel, Shuman Tristan, Shobe Justin, Biane Jeremy, Song Weilin, Wei Brandon, Veshkini Michael, La-Vu Mimi, Lou Jerry, Flores Sergio E, Kim Isaac, Sano Yoshitake, Zhou Miou, Baumgaertel Karsten, Lavi Ayal, Kamata Masakazu, Tuszynski Mark, Mayford Mark, Golshani Peyman, Silva Alcino J
Departments of Neurobiology, Psychiatry &Biobehavioral Sciences and Psychology, Integrative Center for Learning and Memory, Brain Research Institute, University of California, Los Angeles, California 90095, USA.
Departments of Neurology and Psychiatry &Biobehavioral Sciences, Integrative Center for Learning and Memory, Brain Research Institute, University of California, Los Angeles, California 90095, USA.
Nature. 2016 Jun 2;534(7605):115-8. doi: 10.1038/nature17955. Epub 2016 May 23.
Recent studies suggest that a shared neural ensemble may link distinct memories encoded close in time. According to the memory allocation hypothesis, learning triggers a temporary increase in neuronal excitability that biases the representation of a subsequent memory to the neuronal ensemble encoding the first memory, such that recall of one memory increases the likelihood of recalling the other memory. Here we show in mice that the overlap between the hippocampal CA1 ensembles activated by two distinct contexts acquired within a day is higher than when they are separated by a week. Several findings indicate that this overlap of neuronal ensembles links two contextual memories. First, fear paired with one context is transferred to a neutral context when the two contexts are acquired within a day but not across a week. Second, the first memory strengthens the second memory within a day but not across a week. Older mice, known to have lower CA1 excitability, do not show the overlap between ensembles, the transfer of fear between contexts, or the strengthening of the second memory. Finally, in aged mice, increasing cellular excitability and activating a common ensemble of CA1 neurons during two distinct context exposures rescued the deficit in linking memories. Taken together, these findings demonstrate that contextual memories encoded close in time are linked by directing storage into overlapping ensembles. Alteration of these processes by ageing could affect the temporal structure of memories, thus impairing efficient recall of related information.
最近的研究表明,一个共享的神经集合可能会将在时间上编码相近的不同记忆联系起来。根据记忆分配假说,学习会引发神经元兴奋性的暂时增加,这会使后续记忆的表征偏向于编码第一个记忆的神经元集合,以至于回忆一个记忆会增加回忆另一个记忆的可能性。在这里,我们在小鼠身上发现,一天内获得的两种不同情境所激活的海马体CA1集合之间的重叠程度,高于它们被一周时间隔开时的重叠程度。多项研究结果表明,这种神经元集合的重叠将两种情境记忆联系了起来。首先,当两种情境在一天内被获得时,与一种情境配对的恐惧会转移到一个中性情境中,但在一周时间跨度内则不会。其次,第一种记忆在一天内会增强第二种记忆,但在一周时间跨度内则不会。已知CA1兴奋性较低的老年小鼠,不会表现出集合之间的重叠、情境之间的恐惧转移或第二种记忆的增强。最后,在老年小鼠中,在两种不同的情境暴露期间增加细胞兴奋性并激活CA1神经元的一个共同集合,挽救了记忆联系方面的缺陷。综上所述,这些研究结果表明,在时间上编码相近的情境记忆通过将存储导向重叠集合而被联系起来。衰老对这些过程的改变可能会影响记忆的时间结构,从而损害对相关信息的有效回忆。