A knockin neurotensin receptor 1 (Ntsr1)Flp mouse line is developed and validated for intersectional targeting of Ntsr1-expressing neurons, establishing Ntsr1Flp as a versatile driver for scalable Boolean targeting.
Abstract
Precise genetic access to molecularly defined neuronal subpopulations is essential for dissecting circuit heterogeneity. We developed and validated a knockin neurotensin receptor 1 (Ntsr1)Flp mouse line for intersectional targeting of Ntsr1-expressing neurons. Following delivery of Flp-dependent adeno-associated viral (AAV) reporters, robust recombination was observed throughout the midbrain and several other brain regions. A subset of Ntsr1+ neurons in the substantia nigra and ventral tegmental area lacked dopaminergic markers, indicating that midbrain Ntsr1 populations comprise both dopaminergic and non-dopaminergic neurons. Systemic delivery of Cre- and Flp-dependent reporters in complementary dual-recombinase configurations revealed configuration-dependent differences in dopaminergic targeting, which was supported by matched same-gene controls (DatCre;DatFlp). Finally, a dual-recombinase-dependent taCaspase-3 construct enabled selective ablation of midbrain dopamine neurons in vivo, establishing Ntsr1Flp as a versatile driver for scalable Boolean targeting.
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