Fig. 6: DBS reduced grooming-associated neurons in the mOFC of SAPAP3^−/−, as validated with optogenetics.

a Behavior-associated neurons classified as grooming, locomotion, grooming and locomotion, or not-associated neurons using Bayesian ANOVAs (example animal displayed). Raster plot of the deconvolved calcium events of all behavior-associated neurons across time (top). Histograms show the number of binned calcium events for grooming-associated (top, brown), locomotion-associated (middle, pink), and not-associated (bottom, gray) neurons per behavioral period (i.e., grooming, locomotion, or inactive). b In each recorded cortical and striatal region, we detected grooming-, locomotion-, and grooming&locomotion-associated neurons (percentage of grooming-associated neurons depicted in donut charts). c DBS recruited grooming-associated neurons in a dose-dependent manner in mOFC (top). DBS did recruit not-associated neurons dose-dependently in all recorded cortical regions (bottom) (SAPAP3^−/−: lOFC (n = 6), mOFC (n = 5), PL (n = 5), M2 (n = 5), DS (n = 4), VS (n = 5); WT: lOFC (n = 5), mOFC (n = 5), PL (n = 5), M2 (n = 4), DS (n = 5), VS (n = 4). d DBS reduced the number of grooming-associated neurons in mOFC consistently across DBS-parameter experiments (arrow). e Schematic of bilateral optogenetic stimulation of the mOFC (n = 7), lOFC (n = 5), and M2 (n = 5) with ChETA (yellow elliptic shapes), and mOFC (n = 5) with mCherry (red elliptic shapes) in SAPAP3^−/−, projected on the Allen Reference Atlas - Mouse Brain¹⁰¹. Horizontal elliptic shapes represent the tip of the implanted optical fibers. f Reduced grooming during 5 Hz optogenetic stimulation of ChETA-expressing neurons in the mOFC (n = 7) (left). Quantification of reduced grooming (dots are individual animals) (right). g mOFC photostimulation-induced reduction of grooming using 5, 15, and 120 Hz stimulation frequencies, where blocking the optic fibers abolished the effects on grooming. No effect of photostimulation on grooming was found in control animals (injected with stable fluorophore in mOFC), or after activating lOFC or M2. Data are mean ± SEM.