Fig. 3: Sex differences in selectivity of social and nonsocial neural representations of choice.

Normalized fluorescence of an example neuron significantly modulated by social choice aligned to social choice (a) compared to that of an example neuron significantly modulated by social reward aligned to social choice (b). Normalized fluorescence of an example neuron significantly modulated by sucrose choice aligned to sucrose choice (c) compared to that of an example neuron significantly modulated by sucrose reward aligned to sucrose choice (d). Top row shows average fluorescence ± SEM. Bottom row shows a heatmap of normalized fluorescence on each trial aligned to choice (dashed line at zero indicates choice onset) and sorted by reward latency (dark dotted line indicates reward onset). mPFC choice neurons are largely non-overlapping in their responsiveness to social and sucrose choice in both male (e) and female (f) mice (% non-overlapping, male: 83.82%, n = 57/68; female: 93.02%, n = 80/86). g mPFC population activity accurately decoded the subsequent choice earlier in female (green) mice relative to male (purple) mice indicated by shaded gray region. Unpaired t test (−3.0 to −2.5 s: p = 0.0027, −2.5 to −2.0 s: p = 0.0032, −2.0 to −1.5 s: p = 0.019). Choice decoding accuracy in female and male mice becomes equivalent at 1.5 s before choice port entry and both are greater than chance decoding accuracy (colored asterisks and bolded lines indicate where choice decoding is significantly greater than chance). Shaded error regions indicate ± SEM. Dashed line at zero indicates choice port entry. h mPFC population activity in female mice more accurately decoded the choice made on a particular trial compared to male mice. Unpaired t test (p = 0.0090). i mPFC population activity in a 3 s window around social and sucrose choice was equivalently sufficient to decode the sex of the animal and decoded with significantly higher accuracy than shuffled data (dashed line) on both trial types. Unpaired t test (social versus sucrose: p = 0.19; social versus shuffled: p = 2.08*10⁻¹⁹; sucrose versus shuffled: p = 6.84*10⁻¹²). j Across all mice, mPFC neural representations resulted in greater decoding accuracy for reward compared to choice. Paired t test (p = 7.90*10⁻⁸). N = 9 male mice, 9 female mice. Trial-averaged population neural activity traces of sucrose (blue) and social (red) trials in male (k, n = 459 neurons, 9 mice) and female (m, n = 423 neurons, 5 mice) mice plotted on the first 3 PCs in state space. Arrowhead indicates direction of time. Filled green circle indicates choice onset. Euclidean distance separating PC-projected population vectors in a 3 s window around choice is significantly greater between social and sucrose trials than within each trial type in both male (l, n = 9 mice) and female (n, n = 6 mice) mice. Paired t test (male: p = 5.76*10⁻⁴; female: p = 0.0048). All decoding was significantly greater than shuffled data, indicated by a dashed line at 50%. Box plot: center line denotes median, box edges indicate the 25th and 75th percentiles and whiskers extend to ±2.7σ. *p < 0.05.