Neuronal signals in the monkey basolateral amygdala during reward schedules

Abstract

The amygdala is critical for connecting emotional reactions with environmental events. We recorded neurons from the basolateral complex of two monkeys while they performed visually cued schedules of sequential color discrimination trials, with both valid and random cues. When the cues were valid, the visual cue, which was present throughout each trial, indicated how many trials remained to be successfully completed before a reward. Seventy-six percent of recorded neurons showed response selectivity, with the selectivity depending on some aspects of the current schedule. After a reward, when the monkeys knew that the upcoming cue would be valid, 88 of 246 (36%) neurons responded between schedules, seemingly anticipating the receiving information about the upcoming schedule length. When the cue appeared, 102 of 246 (41%) neurons became selective, at this point encoding information about whether the current trial was the only trial required or how many more trials are needed to obtain a reward. These cue-related responses had a median latency of 120 ms (just between the latencies in inferior temporal visual area TE and perirhinal cortex). When the monkey was releasing a touch bar to complete the trial correctly, 71 of 246 (29%) neurons responded, with responses in the rewarded trials being similar no matter which schedule was ending, thus being sensitive to the reward contingency. Finally, 39 of 246 (16%) neurons responded around the reward. We suggest that basolateral amygdala, by anticipating and then delineating the schedule and representing reward contingency, provide contextual information that is important for adjusting motivational level as a function of immediate behavior goals.

Figure 1.

Visually cued reward schedule task. A, Visually cued two-trial reward schedule. Time sequence of stimuli in an individual color discrimination trial is shown. Visual stimuli are centered. B, Visual cues.

Figure 2.

Error rates and reaction times in visually cued reward schedule task in both the valid cue and random cue conditions. A, Relationship between monkeys' behavioral performance and the schedule states. The abscissa shows the schedule states. The ordinate shows the proportion of error trials in all trials (left) and mean reaction times (right) in the correct trials. Behavioral performances in the valid cue condition are shown with black symbols, and performances in the random cue condition are shown with gray symbols. The data include all of the recording sessions for each monkey (131 for monkey A and 115 for monkey B). Error bars indicate SE. B, Relationship between monkey's behavioral performance and the cue brightness.

Figure 3.

Histological localization of recorded neurons. Location of recorded neurons in one monkey (monkey A) are plotted in circles with coronal sections positioned at A26, A25, A24, and A23-A22 of the right hemisphere. A26 represents anterior 26 mm in Horsley-Clarke coordinates (namely, distance from the plane having the external auditory meatus). AA, Anterior amygdaloid nuclei; AB, accessory basal nucleus; B, basal nucleus; Ce, central nucleus; L, lateral nucleus; ac, anterior commissure; cd, caudate nucleus; cl, claustrum; lv, lateral ventricle; opt, optic tract; rs, rhinal sulcus; D, dorsal; L, lateral; M, medial; V, ventral.

Figure 4.

Precue activity. A, In the valid cue condition, neuronal activity before the cue presentation increased only in the first trial (i.e., preschedule activity). The abscissa shows times from the cue onset (0 ms, vertical line). The ordinate shows a firing frequency per trial (spikes per second per trial). Each line of the dots represents a trial in the task. The earliest trial is placed at the bottom. Each curve shows instantaneous firing frequency averaged over all trials and smoothed with a Gaussian filter (σ = 20 ms). The one-, two-, and three-trial schedules are placed on the top, middle, and bottom rows, respectively. Progress in each schedule goes from left to right. The rewarded trials are on the diagonal. The gray triangles pointing down indicate the time when the visual cue and the blue fixation spot disappeared in the previous trial. The black triangles pointing down show the time of reward apparatus activation at the previous trial. The median latency of the preschedule activity from the preceding reward apparatus activation was 742 ms (interquartile range, 451-1018 ms). B, In the random cue condition, preschedule activity disappeared.

Figure 5.

A, B, Strength of precue activity of a neuronal population in the valid cue (A; n = 88) and random cue (B; n = 68) conditions. In the box plots, middle line indicates the median; notches indicate the 95% confidence interval. Whiskers extend to the most extreme data point that is not >1.5 times the interquartile range. The strength of preschedule activity (i.e., 1/1, 1/2, and 1/3 states) was significantly larger in the valid cue condition (A) than in the random cue condition (B; Wilcoxon's test, p < 0.0001).

Figure 6.

Time course of the effect of either the three first cues or three non-first cues on the responses around the cue presentation measured by single-factor ANOVA. The abscissa shows time from the cue onset relative to the end of 350 ms analysis window. A, Number of neurons that showed significant selectivity across the three first or non-first cues (single-factor ANOVAs, p < 0.01). The solid vertical line shows the cue onset. The largest number of neurons (86) with a significant differential activity was found in the 85-435 ms time window after cue onset. Starting with the time window from -185 to 165 ms after the cue onset, the number of cells with significant differential response increased to 12 (a number significantly different from chance; χ² test, p < 0.01). B, Mean percentage response variance explained for 102 neurons that showed at least three consecutive time windows with significant selectivity across the three first cues or the three non-first cues (single-factor ANOVAs, p < 0.01). The gray curves show SE of the percentage response variance explained. The largest average variance was explained in the time window from 105 to 455 ms after cue onset (33 ± 2%, mean ± SE; n = 102).

Figure 7.

Cue-related response that delineates the shortest schedule length. A, In the valid cue condition, this neuron showed unstable preschedule activity starting before the cue onset (0 ms, vertical line). The largest response followed the 1/1 cue. Two comparisons, namely 1/1 versus 1/2 and 1/1 versus 1/3, were significant for this neuron (Tukey's test, p < 0.01). B, In the random cue condition, none of the comparisons between responses to two different first trials (1/1 vs 1/2, 1/1 vs 1/3, and 1/2 vs 1/3) was significantly different (Tukey's test, p > 0.01). C, In the random cue condition, the cue-related responses sorted by brightness did not depend on cue brightness (single-factor ANOVA, p > 0.05). Fiducial marking as in Figure 4.

Figure 8.

Cue-related response. A, In the valid cue condition, after preschedule activity, this neuron showed an excitatory response after the cue onset (0 ms, vertical line) of the one-trial schedule but stopped firing after the cue presentation of the two- or three-trial schedule. In the two- and three-trial schedules, the neuron responded again after the cue onset in the rewarded trials, namely both 2/2 and 3/3. Response latencies are 90 ms for 1/1 cue, 173 for 1/2 cue, 93 for 2/2 cue, 153 for 1/3 cue, and 93 for 3/3 cue. B, In the random cue condition, the neuron showed a small response only to the first cue; however, the response pattern across the cues was significantly different from the responses in the valid cue condition. The strength of the excitatory response in 1/1 was significantly smaller compared with the response in the valid cue condition (t test, p < 0.0001). Response latencies are 145 ms for 1/1 cue, 108 for 1/2 cue, and 113 for 1/3 cue. C, Cue-triggered responses in the random cue condition shown in B were sorted by the brightness of the cue. Brightness value of each cue is shown as percentage brightness (the value 255 is the maximum in 8-bit grayscale and shown as 100%). The strength of the response was modulated by the brightness (single-factor ANOVA, F_(3,88) = 17.7, p < 0.0001), with the brightest cue eliciting the strongest response. The excitatory response to the brightest cue was significantly smaller compared with the response either to the 1/1, 2/2, or 3/3 cues in the valid cue condition (t test, p < 0.001). Fiducial markings as in Figure 4.

Figure 9.

Activity during go/prebar-release period. A, In the valid cue condition, the activity increased gradually as the bar release approached. The vertical lines show time of bar release. The black triangles represent the onset of the go signal. Trials are sorted according to reaction times, and the trial with longest reaction time is placed at the bottom. Responses before bar release were selective for the four levels (trials in schedule before reward; single-factor ANOVA, F_(3,138) = 21.7, p < 0.0001). The responses of the rewarded trials, namely 1/1, 2/2, and 3/3 states, were indistinguishable (F_(2,68) = 0.21, p > 0.05). The activity became stronger as the two- or three-trial schedules progressed (single-factor ANOVA with repeated measures for effect of schedule progress, two-trial schedule, F_(1,22) = 25.4, p < 0.0001; three-trial schedule, F_(2,46) = 9.9, p < 0.0005). B, In the random cue condition, the activity was indistinguishable across the schedule states (single-factor ANOVA, F_(5,116) = 1.17, p = 0.32, p > 0.05). C, Go/prebar-release activity in the random cue condition (B) according to the cue brightness. There was no modulation depending on the cue brightness (single-factor ANOVA, F_(3,118) = 1.30, p > 0.05). Fiducial markings as in Figure 4.

Figure 10.

Strength of go/prebar-release activity of a neuronal population. A, In the valid cue condition, the activity of a neuronal population was larger in rewarded trials (n = 71; paired Wilcoxon's test; ^*p < 0.01; ^**p < 0.001; ^***p < 0.0001). B, In the random cue condition, the population activity was indistinguishable across schedule states (n = 45). The strength of the rewarded trials (1/1, 2/2, and 3/3) was not significantly different between the valid and random cue conditions. Fiducial markings as in Figure 5.

Figure 11.

A-C, Response triggered by reward delivery (1/1, 2/2, and 3/3 states) in the valid cue (A), random cue (B), and free-reward (C) conditions. The vertical lines show time of reward delivery in rewarded trials (black) and equivalent timing without reward delivery in nonrewarded trials (gray). This neuron showed reward-related response in all three conditions. Fiducial markings as in Figure 4.

Figure 12.

Distribution of the neurons that responded to reward in different task conditions. A, Valid cue and/or random cue conditions. B, Valid cue and/or free-reward conditions.

Figure 13.

Response transfer. The black vertical lines show time of reward delivery, and the gray vertical lines show cue onset. A, In the free-reward condition, this neuron showed a response after reward. B, In the valid cue condition, this neuron showed a response to the first cue (1/1, 1/2, and 1/3). The response to the 1/1 cue was larger than the response to the 1/2 cue and 1/3 cue (t test, p < 0.005). Fiducial markings as in Figure 4.