Extended Data Fig. 7: Plasticity at OFC–striatum synapses correlates with compulsive oDASS. | Nature

Extended Data Fig. 7: Plasticity at OFC–striatum synapses correlates with compulsive oDASS.

From: Stochastic synaptic plasticity underlying compulsion in a model of addiction

Extended Data Fig. 7

a, Average of 10 sweeps for AMPAR EPSCs recorded at −70 mV and for EPSCs recorded at +40 mV in slices from renouncing and persevering mice, with or without SPN identification with tdTomato. NMDA amplitude was analysed 20 ms after the peak of the EPSC recorded at +40 mV. The AMPAR/NMDAR ratio for every recorded neuron as a function of perseverance, data are mean ± s.e.m. per animal and correlation (Pearson’s r = 0.84, P < 0.0001; n = 127 cells from 16 mice). Data are mean AMPAR/NMDAR ratio for renouncing and persevering mice (ANOVA followed by two-sided t-test: t17 = 3.13, *P = 0.007 and t19 = 3.53; *P = 0.002 for tdTomato+ and tdTomato, respectively (n = 8 and 11 mice; 9 and 12 cells); t85 = 6.68, *P < 0.0001, renouncing versus persevering for non-identified neurons (42 and 45 cells, respectively)). Data are mean AMPAR/NMDAR ratio for naive mice and for mice yoked to renouncing or persevering mice, with Drd1a–tdTomato identification (naive mice, n = 14 tdTomato+ cells from 5 mice and n = 12 tdTomato cells from 7 mice; mice yoked to renouncing mice, n = 6 tdTomato+ cells from 2 mice and n = 9 tdTomato cells from 2 mice; mice yoked to persevering mice, n = 6 tdTomato+ cells from 2 mice and n = 8 tdTomato cells from 2 mice). b, Average of 10 sweeps for AMPAR EPSCs recorded at −70 mV, with two short light pulses spaced with a 76-ms interval in slices from renouncing and persevering mice, with or without SPN identification using tdTomato. PPR is the ratio of the amplitudes of the second EPSC over the first. PPR for every recorded neuron as a function of perseverance, mean ± s.e.m. per animal and correlation (Pearson’s r = −0.77, P < 0.0001; n = 137 cells from 16 mice). Data are mean PPR for renouncing and persevering mice (ANOVA followed by two-sided t-test: t23 = 3.97, *P = 0.0005 and t22 = 1.72, P = 0.183 for tdTomato+ and tdTomato, respectively (n = 9 and 15 mice; 9 and 16 cells); t86 = 5.66, *P < 0.0001, renouncing versus persevering for non-identified neurons (n = 38 and 50 cells, respectively)). Data are mean PPR for naive mice and for mice yoked to renouncing or persevering mice, with Drd1a–tdTomato identification (naive mice, n = 13 tdTomato+ cells from 5 mice and n = 11 tdTomato cells from 7 mice; mice yoked to renouncing mice, n = 6 tdTomato+ cells from 2 mice and n = 10 tdTomato cells from 2 mice; mice yoked to persevering mice, n = 7 tdTomato+ cells from 2 mice and n = 8 tdTomato cells from 2 mice). c, Left, average of 10 sweeps for AMPAR EPSCs recorded at −70, 0 and +40 mV in slices from renouncing and persevering mice, with or without SPN identification using tdTomato. The rectification of the AMPAR EPSCs was calculated as the ratio of the chord conductance calculated at negative potential divided by chord conductance at positive potential. Middle, rectification index for every recorded neuron as a function of perseverance, mean ± s.e.m. per animal and correlation (Pearson’s r = 0.008, P = 0.971; n = 121 cells from 16 mice). Right, rectification index for renouncing and persevering in tdTomato+ or tdTomato cells (8 and 11 mice; 9 and 11 cells) and in unidentified SPNs (42 and 40 cells, respectively). Data are mean rectification index for naive mice and for mice yoked to renouncing or persevering mice with Drd1a–tdTomato identification (naive mice, n = 13 tdTomato+ cells from 5 mice and n = 11 tdTomato cells from 7 mice; mice yoked to renouncing mice, n = 6 tdTomato+ cells from 2 mice and n = 9 tdTomato cells from 2 mice; mice yoked to persevering mice, n = 7 tdTomato+ cells from 2 mice and n = 8 tdTomato cells from 2 mice). d, Average of 10 sweeps for EPSCs recorded at −70 mV and IPSCs recorded at 0 mV in slices from renouncing and persevering mice and in slices from naive mice. Five pulses were given at different frequencies (5, 10, 20 and 40 Hz) and the charge transfer was measured (area under the curve). The excitatory/inhibitory ratio (E/I) was calculated as the ratio charge transfer for EPSCs over IPSCs. The charge transfer of EPSCs was higher in slices from persevering mice at low frequencies (ANOVA followed by two-sided t-test: t27 = 4.75, *P < 0.0001; t27 = 3.75, *P = 0.0007; t27 = 2.37, P = 0.057; t27 = 1.64, P = 0.306 for 5, 10, 20 and 40 Hz, respectively (17 and 12 cells)). The charge transfer of IPSCs was not different between persevering and renouncing mice (17 and 12 cells, respectively). The ratio of charge transfer for EPSCs over IPSCs was higher in slices from persevering mice (ANOVA followed by two-sided t-test: t27 = 6.22, *P < 0.0001; t27 = 4.39, *P < 0.0001; t27 = 4.07, P = 0.0002; t27 = 3.67, P = 0.001 for 5, 10, 20 and 40 Hz, respectively (17 and 12 cells)). Measurements were obtained from four renouncing mice, three persevering mice and three naive mice. e, Average of 10 sweeps for AMPAR EPSCs in the presence of D-AP5 (50 μM) and NMDAR EPSCs isolated by subtraction for oDASS mice and for naive mice. Mean AMPAR/NMDAR ratio, PPR and rectification index for naive and oDASS mice (*P < 0.05 for t-test comparing naive/oDASS). Each dot represents the mean ± s.e.m. for all cells obtained in a given mouse. Recordings were obtained from six naive mice and seven oDASS mice (PPR: 48 cells from oDASS mice compared to 29 cells from naive mice; rectification index: 52 cells from oDASS mice compared to 24 cells from naive mice; AMPAR/NMDAR ratio with pharmacological isolation: 42 cells from oDASS mice compared to 23 cells from naive mice; AMPAR/NMDAR ratio without pharmacological isolation: 52 cells from oDASS mice compared to 26 cells from naive mice). Scale bars, 200 pA, 50 ms. Data are mean ± s.e.m. See Supplementary Table 1 for complete statistics.

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