Project description:LncRNAs are involved in critical processes for cell homeostasis and function. However, it remains largely unknown whether and how the transcriptional regulation of long noncoding RNAs results in activity-dependent changes at the synapse and facilitate formation of long-term memories. Here, we report the identification of a novel lncRNA, SLAMR, that becomes enriched in CA1- but not in CA3-hippocampal neurons upon contextual fear conditioning. SLAMR is transported to dendrites via the molecular motor KIF5C and recruited to the synapse in response to stimulation. Loss of function of SLAMR reduced dendritic complexity and impaired activity-dependent changes in spine structural plasticity. Interestingly, the gain of function of SLAMR enhanced dendritic complexity, and spine density through enhanced translation. Analyses of the SLAMR interactome revealed its association with CaMKIIa protein through a 220-nucleotide element and its modulation of CaMKIIa activity. Furthermore, loss-of-function of SLAMR in CA1 selectively impairs consolidation but neither acquisition, recall, nor extinction of fear memory and spatial memory. Together, these results establish a new mechanism for activity dependent changes at the synapse and consolidation of contextual fear memory.
Project description:The consolidation of contextual fear memories requires the crosstalk among multiple brain regions, including the hippocampus and amygdala. Despite the advance in single cell transcriptomic techniques, tracing the dynamic gene expression across the hippocampal-amygdala circuit remain challenging. Here we integrated high resolution spatial transcriptomics with single nuclei multi-omics techniques to systematically investigate the spatiotemporally transcriptional programs across the hippocampal-amygdala circuit during the encoding and retrieval of contextual fear memory. It reveals highly dynamic gene expression in the subregions of hippocampus and amygdala. Our data provide new insights into the transcriptional programs underlying consolidation of memory.
Project description:Post-learning sleep plays an important role in hippocampal memory processing, including contextual fear memory (CFM) consolidation. Here, we used targeted recombination in activated populations (TRAP) to label context-encoding engram neurons in the hippocampal dentate gyrus (DG) and assessed reactivation of these neurons during post-learning sleep. We find that post-learning sleep deprivation (SD), which impairs CFM consolidation, selectively disrupts reactivation in inferior blade DG engram neurons. This change was linked to more general suppression of neuronal activity markers in the inferior, but not superior, DG blade by SD. To further characterize how learning and subsequent sleep or SD affect these (and other) hippocampal subregions, we used subregion-specific spatial profiling of transcripts and proteins. We found that transcriptomic responses to sleep loss differed greatly between hippocampal regions CA1, CA3, and DG inferior blade, superior blade, and hilus. Critically, learning-driven transcriptomic changes, measured 6 h following contextual fear learning, were limited to the two DG blades, differed dramatically between the blades, and were absent from all other regions. Similarly, protein abundance in these hippocampal subregions were differentially impacted by sleep vs. SD and by prior learning, with the majority of alterations to protein expression restricted to DG. Together, these data suggest that the DG plays an essential role in the consolidation of hippocampal memories, and that the effects of sleep and sleep loss on the brain are highly subregion-specific, even within the DG itself.
Project description:Post-learning sleep plays an important role in hippocampal memory processing, including contextual fear memory (CFM) consolidation. Here, we used targeted recombination in activated populations (TRAP) to label context-encoding engram neurons in the hippocampal dentate gyrus (DG) and assessed reactivation of these neurons during post-learning sleep. We find that post-learning sleep deprivation (SD), which impairs CFM consolidation, selectively disrupts reactivation in inferior blade DG engram neurons. This change was linked to more general suppression of neuronal activity markers in the inferior, but not superior, DG blade by SD. To further characterize how learning and subsequent sleep or SD affect these (and other) hippocampal subregions, we used subregion-specific spatial profiling of transcripts and proteins. We found that transcriptomic responses to sleep loss differed greatly between hippocampal regions CA1, CA3, and DG inferior blade, superior blade, and hilus. Critically, learning-driven transcriptomic changes, measured 6 h following contextual fear learning, were limited to the two DG blades, differed dramatically between the blades, and were absent from all other regions. Similarly, protein abundance in these hippocampal subregions were differentially impacted by sleep vs. SD and by prior learning, with the majority of alterations to protein expression restricted to DG. Together, these data suggest that the DG plays an essential role in the consolidation of hippocampal memories, and that the effects of sleep and sleep loss on the brain are highly subregion-specific, even within the DG itself.
Project description:Quantitative proteomic analysis was used to identify the proteins associated with a formation of fear memory in mice. The proteins from the hippocampal region were isolated from three groups of trained aminals representing aquisition, consolidation and retrieval of a contextual fear conditioning. The samples were digested by trypsin, analyzed by LC-MSMS followed by protein identification and label-free quantitation using MaxQuant 1.3.0.5. Each group consisted of three individuals and each sample was processed in two technical replicates.
Project description:The goal of our study was to assess whether the experience can regulate specific lncRNAs within the hippocampus and their role in associative memory. To address this, we carried out unbiased analyses of gene expression in CA1-hippocampal neurons to identify lncRNA changes induced by contextual fear conditioning (CFC).