Figure 8. Restricted telencephalic excitatory neuron deletion of Neurexin1α produces a deficit in fast peak activity in p-dSPNs of the DMS.

(A and B) PSTH of ΔF/F for Nex-control (Nrxn1α^+/+; Nex^Cre/+, n = 7, gray) and Nex-Nrxn1α^cKO (Nrxn1α^fl/fl; Nex^Cre/+, n = 6, purple) mice, respectively, aligned to initiation event (segregated by outcome on t−1). Shaded region corresponds to the difference in the preinitiation integral following large and small reward outcomes. (C) There is no statistically significant difference between Nex-control and Nex-Nrxn1α^cKO in the Δpre-initiation integral of large versus small rewards (two-sample t-test, n.s., p=0.084). (D and E) PSTH of ΔF/F for control and mutant animals, respectively, in the fast peak phase of preinitiation activity. (F) Nex-Nrxn1α^cKO exhibit smaller disparity in fast peak signals after unique reward outcomes, as evidenced by significant effect of genotype on Δpre-initiation slope of the fast peak (two-sample t-test, *p=0.025). (G) This difference in Δpre-initiation slope arises from a blunted GCamp response in mutants to large reward outcomes (two-way RM ANOVA). (H) Modeling Ca²⁺ signal dynamics as function of reward variables (blue), prior/future choice (gold), and lagging regressors (light blue) to capture prior circuit states. Value modulation of fast peak activity is blunted in Nex-Nrxn1α^cKO mice (highlighted red box), while other components of the signal remain intact. Slow ramping is largely intact in mutant animals. All data represented as mean ± SEM.

Figure 8—figure supplement 1. Retrograde labeling strategy does not alter excitatory or inhibitory basal synaptic transmission.

(A, Left) Experimental schematic where putative dSPNs are labeled with either retroAAV2.

EF1α−3xFLAG-Cre (together with AAV5.EF1α.DIO::tdTOM in striatum for visualization of retrogradely labeled neurons) or retroAAV2.hSyn-GFP-ΔCre (an enzymatically inactive truncated version of Cre) in the SNr. (A, right) Visualization of infected p-dSPNs for acute slice whole cell recordings. (B) No difference in mIPSC amplitude or frequency was noted between Cre and ΔCre viral constructs. (C) Schematic to test the effect of adult retrograde Cre expression on excitatory synaptic connectivity to p-dSPNs. (D) No difference in mEPSC amplitude or frequency was noted between Cre and ΔCre viral constructs. B and D analyzed by t-test. Data represented as mean ± SEM.