The Skaggs Graduate School of Chemical and Biological Sciences, Scripps Research Institute, La Jolla, CA, 92037, USA.
Department of Neuroscience, The Scripps Research Institute, Jupiter, FL, 33458, USA.
Mol Brain. 2021 Nov 8;14(1):162. doi: 10.1186/s13041-021-00873-9.
Molecular and cellular mechanisms underlying the role of the prelimbic cortex in contextual fear memory remain elusive. Here we examined the kinesin family of molecular motor proteins (KIFs) in the prelimbic cortex for their role in mediating contextual fear, a form of associative memory. KIFs function as critical mediators of synaptic transmission and plasticity by their ability to modulate microtubule function and transport of gene products. However, the regulation and function of KIFs in the prelimbic cortex insofar as mediating memory consolidation is not known. We find that within one hour of contextual fear conditioning, the expression of KIF3B is upregulated in the prelimbic but not the infralimbic cortex. Importantly, lentiviral-mediated knockdown of KIF3B in the prelimbic cortex produces deficits in consolidation while reducing freezing behavior during extinction of contextual fear. We also find that the depletion of KIF3B increases spine density within prelimbic neurons. Taken together, these results illuminate a key role for KIF3B in the prelimbic cortex as far as mediating contextual fear memory.
在背景性恐惧记忆中，前额皮质发挥作用的分子和细胞机制仍然难以捉摸。在这里，我们研究了在介导背景性恐惧（一种联想记忆形式）中发挥作用的驱动蛋白家族分子马达蛋白（KIFs）。KIFs 通过调节微管功能和基因产物的运输，作为突触传递和可塑性的关键介质发挥作用。然而，迄今为止，尚不清楚 KIFs 在介导记忆巩固方面的调节和功能。我们发现，在进行背景性恐惧条件反射后的一个小时内，KIF3B 的表达在前额皮质而非下边缘皮质中上调。重要的是，在消退背景性恐惧时，通过慢病毒介导的前额皮质 KIF3B 敲低会导致巩固缺陷，同时减少冻结行为。我们还发现，KIF3B 的耗竭会增加前额皮质神经元中的棘突密度。综上所述，这些结果表明 KIF3B 在介导背景性恐惧记忆方面在前额皮质中发挥着关键作用。
