Elucidating memory in the brain via single‐cell transcriptomics

Abstract

Understanding the neurobiology of memory is a core goal of neuroscience, and has critical implications for understanding and treating memory-related disorders. Memories have classically been viewed as spatially distributed across the brain (Josselyn et al., 2015;Lashley, 1950), although individual brain regions within these broader networks can make specialized contributions to memory (Vetere et al., 2017). Of particular note are two interconnected brain regions of the medial temporal lobe-the hippocampus and the amygdala-that are indispensable for many different forms of memory

Neuronal cell types, projections, and spatial organization of the central amygdala

“…From a technical standpoint, mFISH also allows higher sensitivity of detection relative to scRNA-seq, circumventing issues of scRNA-seq drop-out. 25 , 46 , 47 , 48 , 49 Ultimately, the general concordance across methodologies for our derived cell-type assignments illustrates that the CEA can be well-captured by a low-dimensional representation in gene-expression space, and that our derived cell type definitions encompass the spatial extent of the CEA.…”

“…Although a variety of work has examined CEA cell types using these a priori marker genes or bulk transcriptional profiling, 14 , 21 , 22 , 23 , 24 to date no published work has examined CEA organization from a whole-genome perspective at a single-cell resolution. Defining cell types at this fine level of granularity is likely to provide a more complete understanding of the cell-type organization of the CEA (for review, see 25 , 26 ): which may validate whether known marker genes capture all cell types, or conversely identify new cell types and organizational principles within the CEA. 27 , 28 In either case, such results can provide a cell-type framework for integrating spatial organization with other structural and functional properties.…”

Post-learning micro- and macro-structural neuroplasticity changes with time and sleep

“…Besides MRI techniques, the advancement and refining of other techniques over the years might also help to gain insight in the processes unfolding during learning. At the molecular level, transcriptomic methods allow the quantification of single gene's expression by accessing RNA levels, making them a prominent, reliable and unbiased tool for to identification of the cells and molecules participating in memory processes [131]. Two main approaches coexist to assess gene expression.…”

“…However, it allows identifying at the whole-genome scale all RNA transcripts, hence allowing to measure gene expression levels in an unbiased and accurate way. The combination of both methods makes it possible to sequence the entire transcriptome, without losing the organizational pattern [131]. Using these methods, genes coding for particular rRNAs [132] and specific proteins regulating synaptic plasticity through the modulation of certain mRNA [133,134] could already be identified, and microRNAs were also found to intervene in synaptic plasticity and learning (for reviews, see [135,136].…”

Cell types in the mouse amygdala and their transcriptional response to fear conditioning

“…Single-cell transcriptomics was used for detecting more general transcriptional signatures of neuronal activation 18,70 . It has recently been suggested and 1025 gained momentum as a tool for comprehensive and unbiased identification of cellular and molecular substrates of learning and memory 22,23,71 . As a word of caution, however, the approach and our study contain a few limitations.…”