Fig. 4: mPFC neurons differ in social and nonsocial reward response selectivity in a sex-dependent manner.
a In both male (left) and female (right) mice, a larger proportion of mPFC neurons are positively modulated (excited) in response to social reward (male: 28.11%, n = 129/459; female: 31.10%, n = 177/570) compared to those that are negatively modulated (inhibited) by social reward (male: 1.09%, n = 5/459; female: 4.39%, n = 25/570). Proportion z test (male: p < 0.00001; female: p < 0.00001). b In contrast to social reward responses (a), mPFC neurons in male (left) and female (right) mice are more likely to be inhibited (male: 12.42%, n = 57/459; female: 10.53%, n = 60/570) rather than excited (male: 6.75%, n = 31/459; female: 7.02%, n = 40/570) in response to sucrose reward. Proportion z test (male: p = 0.0036; female: p = 0.036). c mPFC reward neurons differ in the selectivity of their reward responsiveness in male mice. Social excite neurons are largely exclusive in their response to social reward (64.34%, n = 83/129), with a significantly smaller subset of social excite neurons also responding to sucrose reward (35.66%, 46/129). Proportion z test (p = 4.08*10−6). In contrast, most sucrose excite neurons also responded to social reward (70.97%, n = 22/31). Around half of sucrose inhibit neurons also responded to social reward (42.11%, n = 24/57). Proportion z test (sucrose excite: p = 9.60*10−4, sucrose inhibit: p = 0.092). d mPFC reward neurons are largely non-overlapping in their reward responsiveness in female mice. Social excite neurons are largely exclusive in their response to social reward (80.62%, n = 104/129), with a significantly smaller subset of social excite neurons also responding to sucrose reward (19.38%, n = 25/129). Proportion z test (p < 0.00001). The majority of sucrose excite neurons (70.0%, n = 28/40) and sucrose inhibit neurons did not respond to social reward (78.3%, n = 47/60). Proportion z test (sucrose excite: p = 3.45*10−4, sucrose inhibit: p = 5.38*10−10). e Largely non-overlapping populations of mPFC neurons respond to social and sucrose reward in both male (n = 73.10%, 125/171) and female (n = 87.75%, 179/204) mice. The populations are more distinct in female mice relative to male mice. Proportion z test (p = 3.11*10−4). f Average responses of social reward excite neurons to social (red) and sucrose (blue) reward in male (left) and female (right) mice. g Average responses of sucrose reward excite neurons to social (red) and sucrose (blue) reward in male (left) and female (right) mice. h Average responses of sucrose reward inhibit neurons to social (red) and sucrose (blue) reward in male (left) and female (right) mice. i Heatmaps of the average fluorescence of mPFC neurons in male (left, n = 129 neurons) and female (right, n = 129 neurons) mice that are significantly excited by social reward aligned to social reward (top row) and sucrose reward (bottom row). Neurons are sorted by the time of peak response to social reward. j Heatmaps of the average fluorescence of mPFC neurons in male (left, n = 31 neurons) and female (right, n = 40 neurons) mice that are significantly excited by sucrose reward aligned to social reward (top row) and sucrose reward (bottom row). Neurons are sorted by the time of peak response to sucrose reward. k Heatmaps of the average fluorescence of mPFC neurons in male (left, n = 57 neurons) and female (right, n = 60 neurons) mice that are significantly inhibited by sucrose reward aligned to social reward (top row) and sucrose reward (bottom row). Neurons are sorted by the time of minimum response to sucrose reward. A row on the top and bottom panels of each heatmap (i, j, k) corresponds to the same neuron. l Comparison of the peak amplitude of responses of social reward excite neurons to social and sucrose reward in male (purple, n = 129 neurons, 9 mice) and female (green, n = 129 neurons, 5 mice) mice shows that these neurons on average have a robust excitatory response to social but not sucrose reward in both sexes. Two-factor ANOVA with sex and trial type as factors (interaction: p = 0.067, sex: p = 0.17, trial type: p = 4.11*10-58) with post-hoc t tests comparing trial type within sex (male: p = 1.20*10−33, female: p = 4.15*10−26). m Comparison of the peak amplitude of responses of sucrose reward excite neurons to social and sucrose reward in male (purple, n = 31 neurons, 9 mice) and female (green, n = 40 neurons, 5 mice) mice shows that sucrose reward excite neurons are selective for sucrose reward in female but not male mice. Two-factor ANOVA with sex and trial type as factors (interaction: p = 0.0042, sex: p = 0.014, trial type: p = 1.87*10−4) with post-hoc t tests comparing trial type within sex (male: p = 0.58, female: p = 4.79*10−9). n Comparison of the peak amplitude of responses of sucrose reward inhibit neurons to social and sucrose reward in male (purple, n = 57 neurons, 9 mice) and female (green, n = 60 neurons, 5 mice) mice shows that these neurons on average have a higher amplitude response to social reward compared to sucrose reward across both sexes. Two-factor ANOVA with sex and trial type as factors (interaction: p = 0.011, sex: p < 0.00001, trial type: p = 0.057) with post-hoc t tests comparing trial type within sex (male: p = 5.48*10−18, female: p = 7.60*10−12).
