A bidirectional corticoamygdala circuit for the encoding and retrieval of detailed reward memories
Wassum, Kate et al. (2021), A bidirectional corticoamygdala circuit for the encoding and retrieval of detailed reward memories , Dryad, Dataset, https://doi.org/10.5068/D1109S
Adaptive reward-related decision making often requires accurate and detailed representation of potential available rewards. Environmental reward-predictive stimuli can facilitate these representations, allowing one to infer which specific rewards might be available and choose accordingly. This process relies on encoded relationships between the cues and the sensory-specific details of the reward they predict. Here we interrogated the function of the basolateral amygdala (BLA) and its interaction with the lateral orbitofrontal cortex (lOFC) in the ability to learn such stimulus-outcome associations and use these memories to guide decision making. Using optical recording and inhibition approaches, Pavlovian cue-reward conditioning, and the outcome-selective Pavlovian-to-instrumental transfer (PIT) test in male rats, we found that the BLA is robustly activated at the time of stimulus-outcome learning and that this activity is necessary for sensory-specific stimulus-outcome memories to be encoded, so they can subsequently influence reward choices. Direct input from the lOFC was found to support the BLA in this function. Based on prior work, activity in BLA projections back to the lOFC was known to support the use of stimulus-outcome memories to influence decision making. By multiplexing optogenetic and chemogenetic inhibition we performed a serial circuit disconnection and found that the lOFCàBLA and BLAàlOFC pathways form a functional circuit regulating the encoding (lOFCàBLA) and subsequent use (BLAàlOFC) of the stimulus-dependent, sensory-specific reward memories that are critical for adaptive, appetitive decision making.
Behavioral analysis. Behavioral data were processed with Microsoft Excel (Microsoft, Redmond, WA). Left and/or right lever presses and/or entries into the food-delivery port were collected continuously for each training and test session. Acquisition of the Pavlovian conditional food-port approach response was assessed by computing an elevation ratio of the rate of entries into the food-delivery port (entries/min) during the CS prior to reward delivery (CS-probe) relative to 2-min baseline periods immediately prior to CS onset [(CS probe entry rate)/(CS probe entry rate + preCS entry rate)]. Data were averaged across trials for each CS and then averaged across the two CSs. We also compared the rate of food-port entries between the CS probe and the preCS baseline periods (see data 1-1a, 3-2a, 4-2a, 5-2a). Press rates on the last day of instrumental training were averaged across levers and compared between groups to test for any differences in the acquisition of lever press responding during instrumental training (see data1-1b, 3-2b, 4-2b, 5-2b). For the PIT test, lever pressing during the 2-min baseline periods immediately prior to the onset of each CS was compared with that during the 2-min CS periods. For both the baseline and CS periods, lever pressing was separated for presses on the lever that, during training, earned the same outcome as the presented cue (i.e., preCS-Same and CS-Same presses) versus those on the other available lever (i.e., preCS-Different and CS-Different presses). To evaluate the influence of CS presentation on lever pressing, we computed an elevation ratio for each lever [(CS-Same presses)/(CS-Same presses + preCS-Same presses)] and [(CS-Different presses)/(CS-Different presses + preCS-Different presses)]. To evaluate the influence of CS presentation on food-port entries, i.e., the conditional goal-approach responses, we also computed an elevation ratio [(CS entries)/(CS entries + preCS entries)]. Data were averaged across trials for each CS and then averaged across the two CSs. We also compared the rate of pressing on each lever and, separately, food-port entries between the CS and preCS baseline periods (see data1-1c-d, 3-2c-d, 4-2c-d, 5-2c-d).
Fiber photometry data analysis. Data were pre-processed using a custom-written pipeline in MATLAB (MathWorks, Natick, MA). Data from the 415 nm isosbestic control channel were used to correct for motion artifacts and photobleaching. Using least-squares linear regression, the 415 signal was fit to the 470 signal. Change in fluorescence (DF/F) at each time point was calculated by subtracting the fitted 415 signal from the 470 signal and normalizing to the fitted 415 data [(470-fitted 415)/fitted 415)] (See Figure 1-2). The DF/F data were then Z-scored [(DF/F - mean DF/F)/std(DF/F)]. Using a custom MATLAB workflow, Z-scored traces were then aligned to CS onset, reward delivery, reward retrieval (first food-port entry after reward delivery), and food-port entries without reward present during the CS probe period (after CS before first reward delivery) during the CS for each trial. Peak magnitude and AUC were calculated on the Z-scored trace for each trial using 3-s pre-event baseline and 3-s post-event windows. Data were averaged across trials and then across CSs. Session data were excluded if no transient calcium fluctuations were detected on the 470 nm channel above the isosbestic channel or if poor linear fit was detected due to excessive motion artifact. To examine the progression in BLA activity across training, we compared data across conditioning sessions 1, 2, 3/4, 5/6, and 7/8. Thus, data from the mid and latter training sessions were averaged across bins of 2 training sessions.
Ex vivo electrophysiology. The number of action potentials evoked by suprathreshold current injection was compared before and during exposure to green light to confirm the inhibitory effect of ArchT in BLA principal neurons. To assess the effect of ArchT activation in lOFCàBLA terminals, the frequency of sEPSCs was compared before and during green light exposure.
National Institutes of Health, Award: DA035443
National Science Foundation