Developmental hyperexcitation of Emx1 pyramidal neurons is distinctive in causing behavioral phenotypes
(A) Schematics of a luminopsin (Luc, luciferase, is tethered to ChR, channelrhodopsin; FP, fluorescent protein). Application of the small molecule substrate coelenterazine (CTZ) results in production of photons and bioluminescent optogenetic activation of the nearby opsin (left). The same molecule is accessible to stimulation by a physical light source for standard fiberoptic optogenetic activation (right).
(B) Experimental design. Heterozygous Cre driver mice (Cre/+) were mated with heterozygous conditional (lox-stop-lox) luminopsin-3 mice (LSL-LMO3/+), generating three groups of control mice and one group of experimental mice expressing LMO3 in cells specified by the Cre driver (Cre-LMO3). All pups of a litter were injected once a day intraperitoneally with CTZ postnatal days 4–14. Inset shows representative example of IVIS imaging of Emx1-LMO3 positive and negative pup and ROIs plotted over time. See also Figures S1 and S2.
(C) Schematics of circuits targeted for developmental hyperexcitation. Color codes are used consistently for C and D: red—Emx1, green—Dlx5/6, purple—Pvalb, orange—DAT.
(D) Adult behavior of developmentally hyperexcited mice. Each group of Cre (DAT, Dlx5/6, Emx1, Pvalb)-LMO3 mice is normalized to their non-LMO3 expressing controls. Bars represent mean ± SEM.
See also Figure S3. N = 5-9 per group. ∗p < .05, see also Table S1.