Fig. 7

LTP of L5PN → Aldh1a1 synaptic transmission mediates delay of gratification. a, Experimental schedules for the generation of mutant mice with the expression of ChR2 in L5PN (L5PN^ChR2) and GFP in Aldh1a1 neurons (Aldh1a1^GFP) and whole-cell patch-clamp recordings of Aldh1a1^GFP neurons in the slices from mice after being tested. b, Delay of gratification enhances excitatory synaptic transmission from L5PN to Aldh1a1 neurons. IPSCs were recorded from Aldh1a1^GFP neurons at a holding potential of 0 mV and evoked by electrical stimulation on GABA inhibitory interneuron axon fibers. EPSCs were recorded from the same Aldh1a1^GFP neurons in the slices at a holding potential of −70 mV and evoked by blue laser light stimulation on L5PN^ChR2 axon terminals. The plot shows the ratio of the mean amplitudes of EPSCs versus IPSCs from the individual recordings (blue circles) and the averages per group (red triangles, mean ± SEM, n = 12 recordings/6 mice/group). c, Paired-pulse facilitation was comparable among groups. EPSCs were recorded from Aldh1a1^GFP neurons and evoked by blue laser light stimulation on L5PN axon fibers with paired pulses at an interval of 50 ms. The ratio of pulse two versus pulse one (P2/P1) of the individual recordings (blue circles) and the averages per group (red triangles) was plotted. Data are the mean ± SEM (n = 12 recordings/6 mice/group). d, Delay of gratification potentiates synaptic transmission. The peak amplitudes of EPSCs in the slices from naïve, SIR, or LDR mice after being tested are normalized to the baseline (defined as 100) and plotted against the time of the recordings. The arrow indicates the time of tetanus, consisting of two trains of 100 Hz stimulation lasting 500 ms at an interval of 10 s. LDR/AP5 indicates that EPSCs are recorded in the slices from LDR mice in the presence of 100 μAP5. e, The normalized EPSCs during the last 5 min recordings (d) in the individual slices (blue circles) and the averages per group (mean ± SEM, n = 11 recordings/6 mice/group) are plotted. f, Experimental schedules show the infusion of 1 μl of 500 μM AP5 or saline into VTA 30 min before each day of the probe trials. g, Blocking L5PN → Aldh1a1 synaptic potentiation reduces the behavioral preference for LDR in the probe trials. The plot shows the percentage of the correct trials with the behavioral options for SIR or LDR of mice given AP5 (green) or saline (blue) at each day of the probe trials (mean ± SEM, n = 9 mice per group). h, Blocking L5PN → Aldh1a1 synaptic potentiation decreases the percentage of LRA visits. The plot shows the percentage of LRA visits with a delay of 0-3 s (blue) or 6-9 s (red) from the individual (circles) mice given AP5 or saline and the averages per group (triangles, mean ± SEM, n = 11 mice per group) at day three of the testing sessions. All statistical data are summarized in Supplementary Table 1