Murthy B K B, Somatakis S, Ulivi A F, Klimmt H, Castello-Waldow T P, Haynes N, Huettl R E, Chen A, Attardo Alessio
Leibniz Institute for Neurobiology, Magdeburg, Germany.
Graduate School of Systemic Neurosciences, Munich, Germany.
Front Behav Neurosci. 2023 Jan 30;16:1072571. doi: 10.3389/fnbeh.2022.1072571. eCollection 2022.
Subpopulations of neurons display increased activity during memory encoding and manipulating the activity of these neurons can induce artificial formation or erasure of memories. Thus, these neurons are thought to be cellular engrams. Moreover, correlated activity between pre- and postsynaptic engram neurons is thought to lead to strengthening of their synaptic connections, thus increasing the probability of neural activity patterns occurring during encoding to reoccur at recall. Therefore, synapses between engram neurons can also be considered as a substrate of memory, or a synaptic engram. One can label synaptic engrams by targeting two complementary, non-fluorescent, synapse-targeted GFP fragments separately to the pre- and postsynaptic compartment of engram neurons; the two GFP fragments reconstitute a fluorescent GFP at the synaptic cleft between the engram neurons, thereby highlighting synaptic engrams. In this work we explored a transsynaptic GFP reconstitution system (mGRASP) to label synaptic engrams between hippocampal CA1 and CA3 engram neurons identified by different Immediate-Early Genes: and . We characterized the expression of the cellular and synaptic labels of the mGRASP system upon exposure to a novel environment or learning of a hippocampal-dependent memory task. We found that mGRASP under the control of transgenic ArcCre labeled synaptic engrams more efficiently than when controlled by viral cFostTA, possibly due to differences in the genetic systems rather than the specific IEG promoters.
神经元亚群在记忆编码过程中表现出活动增强，操纵这些神经元的活动可以诱导记忆的人工形成或消除。因此，这些神经元被认为是细胞印迹。此外，突触前和突触后印迹神经元之间的相关活动被认为会导致它们的突触连接增强，从而增加编码过程中出现的神经活动模式在回忆时再次出现的概率。因此，印迹神经元之间的突触也可以被视为记忆的一种基质，即突触印迹。可以通过将两个互补的、非荧光的、靶向突触的绿色荧光蛋白（GFP）片段分别靶向印迹神经元的突触前和突触后区室来标记突触印迹；这两个GFP片段在印迹神经元之间的突触间隙处重新组装成荧光GFP，从而突出显示突触印迹。在这项工作中，我们探索了一种跨突触GFP重组系统（mGRASP），以标记由不同立即早期基因（ 和 ）鉴定的海马CA1和CA3印迹神经元之间的突触印迹。我们表征了mGRASP系统在暴露于新环境或学习海马依赖性记忆任务时细胞和突触标记的表达。我们发现，在转基因ArcCre控制下的mGRASP比在病毒cFostTA控制下更有效地标记突触印迹，这可能是由于遗传系统的差异而非特定的立即早期基因启动子的差异。
