Thalamocortical transcriptional gates coordinate memory stabilization

Yadav, N., Toader, A. & Rajasethupathy, P. Beyond hippocampus: thalamic and prefrontal contributions to an evolving memory. Neuron 112, 1045–1059 (2024).Article  CAS  PubMed  Google Scholar  Agranoff, B. W. & Klinger, P. D. Puromycin effect on memory fixation in the goldfish. Science 146, 952–953 (1964).Article  ADS  CAS  PubMed  Google Scholar  Flexner, L. B. & Flexner, J. B. Effect of acetoxycycloheximide and of an acetoxycycloheximide-puromycin mixture on cerebral protein synthesis and memory in mice. Proc. Natl Acad. Sci. USA 55, 369–374 (1966).Article  ADS  CAS  PubMed  PubMed Central  Google Scholar  Squire, L. R. & Barondes, S. H. Actinomycin-D: effects on memory at different times after training. Nature 225, 649–650 (1970).Article  ADS  CAS  PubMed  Google Scholar  Igaz, L. M., Vianna, M. R. M., Medina, J. H. & Izquierdo, I. Two time periods of hippocampal mRNA synthesis are required for memory consolidation of fear-motivated learning. J. Neurosci. 22, 6781–6789 (2002).Article  CAS  PubMed  PubMed Central  Google Scholar  Kandel, E. R. The molecular biology of memory storage: a dialogue between genes and synapses. Science 294, 1030–1038 (2001).Article  ADS  CAS  PubMed  Google Scholar  Dash, P. K., Hochner, B. & Kandel, E. R. Injection of the cAMP-responsive element into the nucleus of aplysia sensory neurons blocks long-term facilitation. Nature 345, 718–721 (1990).Article  ADS  CAS  PubMed  Google Scholar  Alberini, C. M., Ghirardi, M., Metz, R. & Kandel, E. R. C/EBP is an immediate-early gene required for the consolidation of long-term facilitation in aplysia. Cell 76, 1099–1114 (1994).Article  CAS  PubMed  Google Scholar  Yin, J. C. et al. Induction of a dominant negative CREB transgene specifically blocks long-term memory in Drosophila. Cell 79, 49–58 (1994).Article  CAS  PubMed  Google Scholar  Bourtchuladze, R. et al. Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein. Cell 79, 59–68 (1994).Article  CAS  PubMed  Google Scholar  Silva, A. J., Kogan, J. H., Frankland, P. W. & Kida, S. CREB and memory. Annu. Rev. Neurosci. 21, 127–148 (1998).Article  CAS  PubMed  Google Scholar  Yin, J. C., Del Vecchio, M., Zhou, H. & Tully, T. CREB as a memory modulator: induced expression of a dCREB2 activator isoform enhances long-term memory in Drosophila. Cell 81, 107–115 (1995).Article  CAS  PubMed  Google Scholar  Bartsch, D., Casadio, A., Karl, K. A., Serodio, P. & Kandel, E. R. CREB1 encodes a nuclear activator, a repressor, and a cytoplasmic modulator that form a regulatory unit critical for long-term facilitation. Cell 95, 211–223 (1998).Article  CAS  PubMed  Google Scholar  Josselyn, S. A. et al. Long-term memory is facilitated by cAMP response element-binding protein overexpression in the amygdala. J. Neurosci. 21, 2404–2412 (2001).Article  CAS  PubMed  PubMed Central  Google Scholar  Barco, A., Alarcon, J. M. & Kandel, E. R. Expression of constitutively active CREB protein facilitates the late phase of long-term potentiation by enhancing synaptic capture. Cell 108, 689–703 (2002).Article  CAS  PubMed  Google Scholar  Lin, H.-W., Chen, C.-C., de Belle, J. S., Tully, T. & Chiang, A.-S. CREBA and CREBB in two identified neurons gate long-term memory formation in Drosophila. Proc. Natl Acad. Sci. USA 118, e2100624118 (2021).Article  CAS  PubMed  PubMed Central  Google Scholar  Lamprecht, R. & LeDoux, J. Structural plasticity and memory. Nat. Rev. Neurosci. 5, 45–54 (2004).Article  CAS  PubMed  Google Scholar  Carlezon, W. A. Jr, Duman, R. S. & Nestler, E. J. The many faces of CREB. Trends Neurosci. 28, 436–445 (2005).Article  CAS  PubMed  Google Scholar  Kandel, E. R. The molecular biology of memory: cAMP, PKA, CRE, CREB-1, CREB-2, and CPEB. Mol. Brain 5, 14 (2012).Article  CAS  PubMed  PubMed Central  Google Scholar  Nader, K. Memory traces unbound. Trends Neurosci. 26, 65–72 (2003).Article  CAS  PubMed  Google Scholar  Alberini, C. M. Mechanisms of memory stabilization: are consolidation and reconsolidation similar or distinct processes? Trends Neurosci. 28, 51–56 (2005).Article  CAS  PubMed  Google Scholar  Dudai, Y. Reconsolidation: the advantage of being refocused. Curr. Opin. Neurobiol. 16, 174–178 (2006).Article  CAS  PubMed  Google Scholar  Wood, M. A., Hawk, J. D. & Abel, T. Combinatorial chromatin modifications and memory storage: a code for memory? Learn. Mem. 13, 241–244 (2006).Article  CAS  PubMed  Google Scholar  Coda, D. M. & Gräff, J. From cellular to fear memory: an epigenetic toolbox to remember. Curr. Opin. Neurobiol. 84, 102829 (2024).Article  CAS  PubMed  Google Scholar  Kandel, E. R., Dudai, Y. & Mayford, M. R. The molecular and systems biology of memory. Cell 157, 163–186 (2014).Article  CAS  PubMed  Google Scholar  Holt, C. E., Martin, K. C. & Schuman, E. M. Local translation in neurons: visualization and function. Nat. Struct. Mol. Biol. 26, 557–566 (2019).Article  CAS  PubMed  Google Scholar  Frankland, P. W. & Bontempi, B. The organization of recent and remote memories. Nat. Rev. Neurosci. 6, 119–130 (2005).Article  CAS  PubMed  Google Scholar  Toader, A. C. et al. Anteromedial thalamus gates the selection and stabilization of long-term memories. Cell 186, 1369–1381.e17 (2023).Article  CAS  PubMed  PubMed Central  Google Scholar  Zeisel, A. et al. Molecular architecture of the mouse nervous system. Cell 174, 999–1014.e22 (2018).Article  CAS  PubMed  PubMed Central  Google Scholar  Yao, Z. et al. A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain. Nature 624, 317–332 (2023).Article  ADS  CAS  PubMed  PubMed Central  Google Scholar  Heumos, L. et al. Pertpy: an end-to-end framework for perturbation analysis. Preprint at bioRxiv https://doi.org/10.1101/2024.08.04.606516 (2024).Setty, M. et al. Characterization of cell fate probabilities in single-cell data with Palantir. Nat. Biotechnol. 37, 451–460 (2019).Article  CAS  PubMed  PubMed Central  Google Scholar  Weiler, P., Lange, M., Klein, M., Pe’er, D. & Theis, F. CellRank 2: unified fate mapping in multiview single-cell data. Nat. Methods 21, 1196–1205 (2024).Article  CAS  PubMed  PubMed Central  Google Scholar  Platt, R. J. et al. CRISPR-Cas9 knockin mice for genome editing and cancer modeling. Cell 159, 440–455 (2014).Article  CAS  PubMed  PubMed Central  Google Scholar  Dudai, Y., Jan, Y. N., Byers, D., Quinn, W. G. & Benzer, S. dunce, A mutant of Drosophila deficient in learning. Proc. Natl Acad. Sci. USA 73, 1684–1688 (1976).Article  ADS  CAS  PubMed  PubMed Central  Google Scholar  Davis, R. L. Physiology and biochemistry of Drosophila learning mutants. Physiol. Rev. 76, 299–317 (1996).Article  CAS  PubMed  Google Scholar  Quinn, W. G., Sziber, P. P. & Booker, R. The Drosophila memory mutant amnesiac. Nature 277, 212–214 (1979).Article  ADS  CAS  PubMed  Google Scholar  Fusi, S., Drew, P. J. & Abbott, L. F. Cascade models of synaptically stored memories. Neuron 45, 599–611 (2005).Article  CAS  PubMed  Google Scholar  Marco, A. et al. Mapping the epigenomic and transcriptomic interplay during memory formation and recall in the hippocampal engram ensemble. Nat. Neurosci. 23, 1606–1617 (2020).Article  CAS  PubMed  PubMed Central  Google Scholar  Santoni, G. et al. Chromatin plasticity predetermines neuronal eligibility for memory trace formation. Science 385, eadg9982 (2024).Article  CAS  PubMed  Google Scholar  Huentelman, M. J. et al. Calmodulin-binding transcription activator 1 (CAMTA1) alleles predispose human episodic memory performance. Hum. Mol. Genet. 16, 1469–1477 (2007).Article  CAS  PubMed  Google Scholar  Teixeira, J. R., Szeto, R. A., Carvalho, V. M. A., Muotri, A. R. & Papes, F. Transcription factor 4 and its association with psychiatric disorders. Transl. Psychiatry 11, 19 (2021).Article  PubMed  PubMed Central  Google Scholar  Liu, H. et al. ASH1L mutation caused seizures and intellectual disability in twin sisters. J. Clin. Neurosci. 91, 69–74 (2021).Article  CAS  PubMed  Google Scholar  Bintu, L. et al. Dynamics of epigenetic regulation at the single-cell level. Science 351, 720–724 (2016).Article  ADS  CAS  PubMed  PubMed Central  Google Scholar  Larsen, S. B. et al. Establishment, maintenance, and recall of inflammatory memory. Cell Stem Cell 28, 1758–1774.e8 (2021).Article  CAS  PubMed  PubMed Central  Google Scholar  Stern, S., Kirst, C. & Bargmann, C. I. Neuromodulatory control of long-term behavioral patterns and individuality across development. Cell 171, 1649–1662.e10 (2017).Article  CAS  PubMed  Google Scholar  Hergenreder, E. et al. Combined small-molecule treatment accelerates maturation of human pluripotent stem cell-derived neurons. Nat. Biotechnol. https://doi.org/10.1038/s41587-023-02031-z (2024).Article  PubMed  PubMed Central  Google Scholar  Campbell, R. R. & Wood, M. A. How the epigenome integrates information and reshapes the synapse. Nat. Rev. Neurosci. 20, 133–147 (2019).Article  CAS  PubMed  PubMed Central  Google Scholar  Mews, P. et al. From circuits to chromatin: the emerging role of epigenetics in mental health. J. Neurosci. 41, 873–882 (2021).Article  CAS  PubMed  PubMed Central  Google Scholar  Grandi, F. C., Modi, H., Kampman, L. & Corces, M. R. Chromatin accessibility profiling by ATAC-seq. Nat. Protoc. 17, 1518–1552 (2022).Article  CAS  PubMed  PubMed Central  Google Scholar  Hrvatin, S. et al. Single-cell analysis of experience-dependent transcriptomic states in the mouse visual cortex. Nat. Neurosci. 21, 120–129 (2018).Article  CAS  PubMed  Google Scholar  Nott, A., Schlachetzki, J. C. M., Fixsen, B. R. & Glass, C. K. Nuclei isolation of multiple brain cell types for omics interrogation. Nat. Protoc. 16, 1629–1646 (2021).Article  CAS  PubMed  PubMed Central  Google Scholar  Azizi, E. et al. Single-cell map of diverse immune phenotypes in the breast tumor microenvironment. Cell 174, 1293–1308.e36 (2018).Article  CAS  PubMed  PubMed Central  Google Scholar  Wolf, F. A., Angerer, P. & Theis, F. J. SCANPY: large-scale single-cell gene expression data analysis. Genome Biol. 19, 15 (2018).Article  PubMed  PubMed Central  Google Scholar  Wolock, S. L., Lopez, R. & Klein, A. M. Scrublet: computational identification of cell doublets in single-cell transcriptomic data. Cell Syst. 8, 281–291.e9 (2019).Article  CAS  PubMed  PubMed Central  Google Scholar  Levine, J. H. et al. Data-driven phenotypic dissection of AML reveals progenitor-like cells that correlate with prognosis. Cell 162, 184–197 (2015).Article  CAS  PubMed  PubMed Central  Google Scholar  Phillips, J. W. et al. A repeated molecular architecture across thalamic pathways. Nat. Neurosci. 22, 1925–1935 (2019).Article  CAS  PubMed  PubMed Central  Google Scholar  Finak, G. et al. MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data. Genome Biol. 16, 278 (2015).Article  PubMed  PubMed Central  Google Scholar  Fang, Z., Liu, X. & Peltz, G. GSEApy: a comprehensive package for performing gene set enrichment analysis in Python. Bioinformatics 39, btac757 (2023).Article  CAS  PubMed  Google Scholar  Glasner, A. et al. Conserved transcriptional connectivity of regulatory T cells in the tumor microenvironment informs new combination cancer therapy strategies. Nat. Immunol. 24, 1020–1035 (2023).Article  CAS  PubMed  PubMed Central  Google Scholar  Dann, E., Henderson, N. C., Teichmann, S. A., Morgan, M. D. & Marioni, J. C. Differential abundance testing on single-cell data using k-nearest neighbor graphs. Nat. Biotechnol. 40, 245–253 (2022).Article  CAS  PubMed  Google Scholar  Keenan, A. B. et al. ChEA3: transcription factor enrichment analysis by orthogonal omics integration. Nucleic Acids Res. 47, W212–W224 (2019).Article  CAS  PubMed  PubMed Central  Google Scholar  Yao, Z. et al. Whole mouse brain transcriptomic cell type atlas — 10x scRNAseq whole brain [dataset]. NeMO https://assets.nemoarchive.org/dat-qg7n1b0 (2023).

View Original Article