A Thalamic Orphan Receptor Drives Variability in Short-Term Memory.
Cell 2020 Oct 15; 183(2):522-536.e19
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.
Hsiao, Kuangfu; Noble, Chelsea; Pitman, Wendy; Yadav, Nakul; Kumar, Suraj; Keele, Gregory R; Terceros, Andrea; Kanke, Matt; Conniff, Tara; Cheleuitte-Nieves, Christopher; Tolwani, Ravi; Sethupathy, Praveen; and Rajasethupathy, Priyamvada, "A Thalamic Orphan Receptor Drives Variability in Short-Term Memory." (2020). Faculty Research 2020. 189.