RT Journal Article
SR Electronic
T1 Spatial and single-cell transcriptomics reveal neuron-astrocyte interplay in long-term memory
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.03.20.533566
DO 10.1101/2023.03.20.533566
A1 Wenfei Sun
A1 Zhihui Liu
A1 Xian Jiang
A1 Michelle B. Chen
A1 Hua Dong
A1 Jonathan Liu
A1 Thomas C. Südhof
A1 Stephen R. Quake
YR 2023
UL http://biorxiv.org/content/early/2023/03/21/2023.03.20.533566.abstract
AB Memory encodes past experiences, thereby enabling future plans. The basolateral amygdala (BLA) is a center of salience networks that underlie emotional experience and thus plays a key role in long-term fear memory formation1, 2. Here we used spatial and single-cell transcriptomics to illuminate the cellular and molecular architecture of the role of the basolateral amygdala in long-term memory. We identified transcriptional signatures in subpopulations of neurons and astrocytes that were memory-specific and persisted for weeks. These transcriptional signatures implicate neuropeptide signaling, mitogen-activated protein kinase (MAPK), brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), ubiquitination pathways, and synaptic connectivity in long-term memory. We also discovered that a neuronal sub-population, defined by increased Penk expression and decreased Tac expression, constitutes the most prominent component of the BLA’s memory engram. These transcriptional changes were observed both with single-cell RNAseq and with single-molecule spatial transcriptomics in intact slices, thereby providing a rich spatial map of a memory engram. The spatial data enabled us to show that this neuronal subpopulation further interacts with spatially related astrocytes that are essential for memory consolidation, indicating that neurons require interactions with astrocytes to encode long term memory.Competing Interest StatementThe authors have declared no competing interest.