A Thalamic Orphan Receptor Drives Variability in Short-Term Memory.
Document Type
Article
Publication Date
10-15-2020
Keywords
JMG
JAX Source
Cell 2020 Oct 15; 183(2):522-536.e19
Volume
183
Issue
2
First Page
522
Last Page
536
ISSN
1097-4172
PMID
32997977
DOI
https://doi.org/10.1016/j.cell.2020.09.011
Abstract
Working memory is a form of short-term memory that involves maintaining and updating task-relevant information toward goal-directed pursuits. Classical models posit persistent activity in prefrontal cortex (PFC) as a primary neural correlate, but emerging views suggest additional mechanisms may exist. We screened ∼200 genetically diverse mice on a working memory task and identified a genetic locus on chromosome 5 that contributes to a substantial proportion (17%) of the phenotypic variance. Within the locus, we identified a gene encoding an orphan G-protein-coupled receptor, Gpr12, which is sufficient to drive substantial and bidirectional changes in working memory. Molecular, cellular, and imaging studies revealed that Gpr12 enables high thalamus-PFC synchrony to support memory maintenance and choice accuracy. These findings identify an orphan receptor as a potent modifier of short-term memory and supplement classical PFC-based models with an emerging thalamus-centric framework for the mechanistic understanding of working memory.
Recommended Citation
Hsiao K,
Noble C,
Pitman W,
Yadav N,
Kumar S,
Keele G,
Terceros A,
Kanke M,
Conniff T,
Cheleuitte-Nieves C,
Tolwani R,
Sethupathy P,
Rajasethupathy P.
A Thalamic Orphan Receptor Drives Variability in Short-Term Memory. Cell 2020 Oct 15; 183(2):522-536.e19