Fig. 4: Optogenetic inhibition of mPFC neurons reduces sucrose preference by impairing learning.

a Experimental design of optogenetic inhibition experiment, in which C57Bl/6 mice (male and female; n = 5 eNpHR mice, n = 6 eYFP mice) were subjected to a 1-h SPT. mPFC pyramidal neurons expressing eNpHR (or eYFP) were inhibited using 589 nm laser light during ON (orange) epochs. b Optogenetic stimulation protocol. Animals were tested in three different sessions (sessions counterbalanced between days), in which no laser light was delivered (baseline session, OFF-OFF-OFF), or light was delivered only during the first or second 20-min epochs (ON-OFF-OFF or OFF-ON-OFF, respectively). c Experimental data, showing % sucrose preference (left), % choices for sucrose (middle) and total licks (right) per 20-min epoch. Individual lines show OFF-OFF-OFF (baseline), ON-OFF-OFF and OFF-ON-OFF sessions. Error bars indicate mean ± SEM. Asterisks indicate significance compared to baseline sessions in paired t-tests; **p < 0.01, *p < 0.05; see Supplementary Table 1 for statistical details. Source data are provided as a Source Data file. d Simulated data showing the predicted % choices for sucrose based on different cognitive impairments during the ON epochs (n = 5 simulated mice). The baseline (OFF-OFF-OFF) session was used to estimate computational parameter values, which were then used to predict how changes in the model parameters affected the % of choices for sucrose in an ON epoch. Displayed are anhedonia (ρ → 1 during ON; left), a learning impairment (α → 0 during ON; middle) and abolished discounting/attraction (η → 0 during ON; right). A learning impairment only impacts observable behavior early in the session when the values of the two bottles has not yet been established. Anhedonia impacts the % of choices for sucrose, regardless of whether this is induced at the beginning or in the middle of the session (see Supplementary Fig. 9 for rationale). A change in the discount/attraction parameter does not impact the simulated % choices for sucrose. Error bars indicate mean ± SEM. Source data are provided as a Source Data file.