Fig. 6: Activation and inhibition of mPFC neurons during the reward period disrupts reward-seeking behavior. | Nature Communications

Fig. 6: Activation and inhibition of mPFC neurons during the reward period disrupts reward-seeking behavior.

From: Sex differences in neural representations of social and nonsocial reward in the medial prefrontal cortex

Fig. 6

a Experimental timeline showing training and optogenetic stimulation schedule. b Schematic of the viral strategy (left panel) used to label mPFC neurons with either channelrhodopsin (ChR2) or GFP (control). Example histology showing ChR2 expression (ChR2 in green, DAPI labeling of cell nuclei in blue) and ferrule placement in the mPFC at 4x magnification (right panel). Scale bar: 500 µm. c Reconstruction of optic ferrule placement in male (left, n = 14 mice) and female (right, n = 14 mice) mice using WholeBrain software84. Each colored dot shows the position of the optic ferrule in the Allen Mouse Brain Common Coordinate Framework. Blue dots indicate ChR2 mice (male: n = 8 mice; female: n = 8 mice), black dots indicate GFP mice (male: n = 6 mice; female: n = 6 mice). Coronal slice is 1.945 mm anterior to bregma. Optogenetic activation of mPFC neurons during the reward period increases reward latency (d, h), reward fails (e, i) and average distance traveled (f, j) on sucrose and social trials compared to GFP controls in both male (d, e, f) and female (h, i, j) mice. Two-factor ANOVA with virus (ChR2/GFP) and trial type (sucrose/social) as factors (d, interaction: p = 0.21, virus: p = 7.52*10−9, trial type: p = 5.62*10−13; e, interaction: p = 6.57*10−6, virus: p = 2.38*10−10, trial type: p = 3.21*10−8; f, interaction: p = 0.12, virus: p = 1.41*10−18, trial type: p = 5.50*10−98; h, interaction: p = 0.064, virus: p = 4.09*10−13, trial type: p = 2.05*10−19; i, interaction: p = 0.0026, virus: p = 1.14*10−9, trial type: p = 0.0002; j, interaction: p = 0.97, virus: p = 2.00*10−11, trial type: p = 9.23*10−114) with post-hoc unpaired t tests comparing virus within trial type (d, sucrose: p = 1.95*10−6, social: p = 5.51*10−5; e, sucrose: p = 2.83*10−8, social: p = 0.0042; f, sucrose: p = 3.67*10−15, social: p = 3.64*10−8; h, sucrose: p = 7.92*10−10, social: p = 3.81*10−7; i, sucrose: p = 9.98*10−7, social: p = 1.63*10−4; j, sucrose: p = 2.71*10−6, social: p = 2.75*10−6). Optogenetic activation of mPFC neurons also caused a decrease in the time spent in the social zone during the reward period when compared to GFP controls in male (g) and female (k) mice. Unpaired t test (male: p = 0.015; female: p = 2.69*10−6). l Schematic of the viral strategy (left panel) used to label mPFC neurons with either GtACR inhibitory opsin (GtACR) or mCherry (control). Example histology showing GtACR expression (GtACR in red, DAPI labeling of cell nuclei in blue) and ferrule placement in the mPFC at 4x magnification (right panel). Scale bar: 500 µm. m Reconstruction of optic ferrule placement in male (left, n = 13 mice) and female (right, n = 13 mice) mice using WholeBrain software84. Each colored dot shows the position of the optic ferrule in the Allen Mouse Brain Common Coordinate Framework. Red dots indicate GtACR mice (male: n = 7 mice; female: n = 7 mice), black dots indicate mCherry mice (male: n = 6 mice; female: n = 6 mice). Coronal slice is 1.945 mm anterior to bregma. Optogenetic inhibition of mPFC neurons during the reward period increases reward latency on both social and sucrose trials compared to mCherry controls in male (n) and female (r) mice. Two-factor ANOVA with virus (GtACR/mCherry) and trial type (sucrose/social) as factors (n, interaction: p = 0.67, virus: p = 0.0004, trial type: p < 0.00001; r, interaction: p = 0.83, virus: p = 2.46*10−8, trial type: p = 2.29*10−12) with post-hoc unpaired t tests comparing virus within trial type (n, sucrose: p = 0.0014, social: p = 0.021; r, sucrose: p = 5.46*10−10, social: p = 0.0014). Optogenetic inhibition also increases the number of social reward fails compared to mCherry controls in male mice (o) and both sucrose and social reward fails in female mice (s). Two-factor ANOVA with virus (GtACR/mCherry) and trial type (sucrose/social) as factors (o, interaction: p = 0.50, virus: p = 0.0039, trial type: p = 0.37; s, interaction: p = 0.055, virus: p = 0.0002, trial type: p = 0.0001) with post-hoc unpaired t tests comparing virus within trial type (o, sucrose: p = 0.13, social: p = 0.0084; s, sucrose: p = 0.002, social: p = 0.026). Optogenetic inhibition of mPFC neurons had no effect on average distance traveled during social or sucrose trials in both sexes. Two-factor ANOVA (p, interaction: p = 0.18, virus: p = 0.16, trial type: p = 3.01*10−106; t, interaction: p = 0.76, virus: p = 0.42, trial type: p = 1.97*10−89). Optogenetic inhibition of mPFC neurons caused a decrease in the time spent in the social zone during the reward period when compared to mCherry controls in male (q) but not female (u) mice. Unpaired t test (male: p = 0.013; female: p = 0.31). *p < 0.05. Box plots: center line denotes median, box edges indicate the 25th and 75th percentiles and whiskers extend to ± 2.7σ.

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