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. 2023 Jul 6;12:e87902. doi: 10.7554/eLife.87902

Figure 4. Impaired dopamine (DA) overflow in DAT::NrxnsKO mice.

(A) Representative traces of electrically evoked DA overflow detected by fast-scan cyclic voltammetry in the ventral striatum, measured in slices prepared from DAT::NrxnsWT and DAT::NrxnsKO mice. (B) Bar graphs showing the average peak DA levels (µM) detected in the ventral striatum (WT = 0.98 ± 0.04 µM and KO = 0.98 ± 0.06 µM). (C) Evaluation of DA overflow kinetics in the ventral striatum estimated by quantifying tau (WT = 0.35 ± 0.02 and KO = 0.42 ± 0.02). (D) Short-term paired-pulse induced plasticity of DA overflow in ventral striatal slices, estimated by calculating (P2-P1/P1) with an inter-pulse interval of 100 ms. The low ratio values reflect the strong paired-pulse depression seen at such release sites in acute brain slices. (E) Representative traces of electrically evoked DA overflows detected by fast-scan cyclic voltammetry in the dorsal striatum. (F) Bar graphs showing the average peak DA levels (µM) detected in the dorsal striatum (WT = 1.33 ± 0.05 µM and KO = 1.35 ± 0.07 µM). (G) Evaluation of DA overflow kinetics in the dorsal striatum, estimated by quantifying tau (WT = 0.36 ± 0.02 s and KO = 0.45 ± 0.03 s). (H) Short-term paired-pulse induced plasticity of DA overflow in dorsal striatal slices, estimated by calculating (P2-P1/P1) with an inter-pulse interval at 100 ms. The low ratio values reflect the strong paired-pulse depression seen at such release sites in acute brain slices. (I) Representative traces of electrically evoked DA overflow detected by fast-scan cyclic voltammetry in the ventral striatum, measured in slices prepared from DAT::NrxnsWT and DAT::NrxnsKO mice in the presence of the nicotinic receptor antagonist DHßE. (J) Bar graphs showing the average peak DA levels (µM) detected in the ventral striatum (WT = 0.47 ± 0.09 µM and KO = 0.24 ± 0.06 µM). (K) Evaluation of DA overflow kinetics in the ventral striatum estimated by quantifying tau (WT = 1.35 ± 0.17 s and KO = 1.63 ± 0.16 s). (L) Short-term paired-pulse induced plasticity of DA overflow in ventral striatal slices, estimated by calculating (P2-P1/P1) with an inter-pulse interval of 100 ms. The low ratio values reflect the strong paired-pulse depression seen at such release sites in acute brain slices. (M) Representative traces of electrically evoked DA overflow detected by fast-scan cyclic voltammetry in the dorsal striatum in the presence of the nicotinic receptor antagonist DHßE. (N) Bar graphs showing the average peak DA levels (µM) detected in the dorsal striatum (WT = 0.43 ± 0.05 µM and KO = 0.24 ± 0.03 µM). (O) Evaluation of DA overflow kinetics in the dorsal striatum, estimated by quantifying tau (WT = 1.37 ± 0.22 s and KO = 1.21 ± 0.24 s). (P) Short-term paired-pulse induced plasticity of DA overflow in dorsal striatal slices, estimated by calculating (P2-P1/P1) with an inter-pulse interval at 100 ms. The low ratio values reflect the strong paired-pulse depression seen at such release sites in acute brain slices. Data are presented as mean ± SEM. Statistical analyses were performed with Student’s t-tests (*p<0.05; **p<0.01).

Figure 4—source data 1. Contains the primary data for Figure 4 and Figure 4—figure supplements 1 and 2.

Figure 4.

Figure 4—figure supplement 1. Detection of activity-dependent dopamine (DA) overflow by fast-scan cyclic voltammetry (FSCV).

Figure 4—figure supplement 1.

(A–D) Representative voltammograms of FSCV recordings performed in ventral striatal (vSTR) or dorsal striatal (dSTR) sections from DAT::NrxnsWT and DAT::NrxnsKO confirming the identity of the electroactive substance as DA. (E) Representative traces of electrically evoked DA levels detected by FSCV in the vSTR, measured in slices prepared from DAT::NrxnsWT and DAT::NrxnsKO mice. (F) Bar graphs showing the average peak DA levels (µM) detected in the vSTR (WT = 0.82 ± 0.05 µM and knock-out [KO] = 0.75 ± 0.06 µM). (G) Evaluation of DA overflow kinetics in the vSTR estimated by quantifying tau (WT = 0.6 ± 0.04 µM and KO = 0.91 ± 0.06 µM). (H) Representative traces of electrically evoked DA levels detected by FSCV in the dSTR. (I) Bar graphs showing the average of peak DA levels (µM) detected in the dSTR (WT = 1.07 ± 0.05 µM and KO = 1.05 ± 0.07 µM). (J) Evaluation of DA overflow kinetics in the dSTR, estimated by quantifying tau (WT = 0.67 ± 0.04 s and KO = 0.72 ± 0.04 s). (K–L) Representative traces of electrically evoked DA levels in the dSTR, measured in slices prepared from DAT::NrxnsWT mice with (red line) and without (black line) dihydro-β-erythroidine hydrobromide (DHβE) (10 µM). (M–P) Representative traces of electrically evoked DA levels detected by FSCV in the vSTR and dSTR after single (black line) or paired-pulse (gray line) stimulation, in the presence of DHβE. Data are presented as mean ± SEM. Statistical analyses were performed with Student’s t-test (*p<0.05; ** p<0.01; ***p<0.001).
Figure 4—figure supplement 2. No change in GABAB receptor modulation of dopamine (DA) release after conditional deletion of all neurexins.

Figure 4—figure supplement 2.

(A) Summary graph of the rise time of electrically evoked DA overflow in the dorsal striatum shows no genotype effect. (B) Summary graph of the rise time of electrically evoked DA overflow in the ventral striatum shows no genotype effect. (C) Plot of relative peak DA overflow and its modulation by the GABAB agonist baclofen in the ventral striatum. No difference between WT KO mice was observed.