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Role of Central Serotonin in Anticipation of Rewarding and Punishing Outcomes: Effects of Selective Amygdala or Orbitofrontal 5-HT Depletion.

Rygula R, Clarke HF, Cardinal RN, Cockcroft GJ, Xia J, Dalley JW, Robbins TW, Roberts AC - Cereb. Cortex (2014)

Bottom Line: To address this apparent discrepancy, the present study determined whether both effects could be found in the same animals by performing localized 5-HT depletions in the amygdala or orbitofrontal cortex (OFC) of a New World monkey, the common marmoset. 5-HT depletion in the amygdala impaired response choice on a probabilistic visual discrimination task by increasing the effectiveness of misleading, or false, punishment and reward, and decreased response suppression in a variable interval test of punishment sensitivity that employed the same reward and punisher. 5-HT depletion in the OFC also disrupted probabilistic discrimination learning and decreased response suppression.Computational modeling of behavior on the discrimination task showed that the lesions reduced reinforcement sensitivity.A novel, unitary account of the findings in terms of the causal role of 5-HT in the anticipation of both negative and positive motivational outcomes is proposed and discussed in relation to current theories of 5-HT function and our understanding of mood and anxiety disorders.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, University of Cambridge, Cambridge CB2 3EB, UK Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3EB, UK Current Address: Affective Cognitive Neuroscience Laboratory, Department of Behavioral Neurobiology and Drug Development, Institute of Pharmacology Polish Academy of Sciences, ul Smetna 12, 31-343 Krakow, Poland.

No MeSH data available.


Related in: MedlinePlus

Lowered 5-HT in the amygdala or OFC impaired probabilistic discrimination and reversal. (A) Number of errors prior to reaching criterion performance (excluding the day on which the criterion was passed), square-root transformed, for each stage. (B) The probability of “obeying” feedback from the preceding trial (i.e., of staying with the previously chosen stimulus following reward, or switching to the alternative stimulus following punishment). Data are from discrimination learning stages (D5–D8) only. The response to “true” (majority) or “false” (minority) feedback is shown separately; the proportion of majority feedback trials was 80% (D5, D6, D8) or 70% (D7). (C) Group mean parameter values from the best-fit computational model of behavior (see text). Points indicate the mean of the posterior distribution of each parameter; error bars are 75% and 95% highest density intervals (HDIs). The computational model was fitted using data from discriminations (D5–D8) only. (D) The probability of “obeying” feedback, as for (B), but calculated using per-subject mean probabilities of “obeying” each kind of feedback, sampled from the best-fit computational model of behavior. The similarity to (B) indicates that the model successfully captured these aspects of behavior, even though the model incorporated no information about the “veracity” of preceding feedback. (E) Group mean differences in parameters from the best-fit computational model of behavior (see text), shown as the mean of the posterior distribution of each comparison parameter, directly sampled using Monte Carlo techniques from the hierarchical Bayesian inference model. Error bars are HDIs as before (orange, 75% HDI excludes zero; red, 95% HDI excludes zero). Percentages are the posterior probabilities that the parameter differs from 0 (width of the largest HDI excluding zero). The computational model was the same as that in (C).
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BHU102F3: Lowered 5-HT in the amygdala or OFC impaired probabilistic discrimination and reversal. (A) Number of errors prior to reaching criterion performance (excluding the day on which the criterion was passed), square-root transformed, for each stage. (B) The probability of “obeying” feedback from the preceding trial (i.e., of staying with the previously chosen stimulus following reward, or switching to the alternative stimulus following punishment). Data are from discrimination learning stages (D5–D8) only. The response to “true” (majority) or “false” (minority) feedback is shown separately; the proportion of majority feedback trials was 80% (D5, D6, D8) or 70% (D7). (C) Group mean parameter values from the best-fit computational model of behavior (see text). Points indicate the mean of the posterior distribution of each parameter; error bars are 75% and 95% highest density intervals (HDIs). The computational model was fitted using data from discriminations (D5–D8) only. (D) The probability of “obeying” feedback, as for (B), but calculated using per-subject mean probabilities of “obeying” each kind of feedback, sampled from the best-fit computational model of behavior. The similarity to (B) indicates that the model successfully captured these aspects of behavior, even though the model incorporated no information about the “veracity” of preceding feedback. (E) Group mean differences in parameters from the best-fit computational model of behavior (see text), shown as the mean of the posterior distribution of each comparison parameter, directly sampled using Monte Carlo techniques from the hierarchical Bayesian inference model. Error bars are HDIs as before (orange, 75% HDI excludes zero; red, 95% HDI excludes zero). Percentages are the posterior probabilities that the parameter differs from 0 (width of the largest HDI excluding zero). The computational model was the same as that in (C).

Mentions: Animals destined to receive either selective 5-HT depletions within the amygdala, OFC, or control surgery did not differ in their ability to learn a series of visual discriminations (one-way ANOVA errors to criterion, F < 1). Nor did they differ in their ability to remember a previously learned visual discrimination (one-way ANOVA errors to criterion, F < 1) postoperatively (mean errors to regain criterion, control 0.61 ± 0.6, 5-HT AMYG 1.8 ± 1.1, 5-HT OFC 0.6 ± 0.7). However, 5-HT depletions in either locus did significantly impair the acquisition and reversal of a series of novel discriminations, as assessed by the number of errors made before attaining criterion performance (Fig. 3A). The depleted groups did not differ from each other, and there was no interaction with discrimination/reversal stage. There were no differences between individual discriminations (despite some differences in reinforcement probability and the aversive outcome) or between individual reversals; unsurprisingly, more errors were made during reversals than during discrimination learning.Figure 3.


Role of Central Serotonin in Anticipation of Rewarding and Punishing Outcomes: Effects of Selective Amygdala or Orbitofrontal 5-HT Depletion.

Rygula R, Clarke HF, Cardinal RN, Cockcroft GJ, Xia J, Dalley JW, Robbins TW, Roberts AC - Cereb. Cortex (2014)

Lowered 5-HT in the amygdala or OFC impaired probabilistic discrimination and reversal. (A) Number of errors prior to reaching criterion performance (excluding the day on which the criterion was passed), square-root transformed, for each stage. (B) The probability of “obeying” feedback from the preceding trial (i.e., of staying with the previously chosen stimulus following reward, or switching to the alternative stimulus following punishment). Data are from discrimination learning stages (D5–D8) only. The response to “true” (majority) or “false” (minority) feedback is shown separately; the proportion of majority feedback trials was 80% (D5, D6, D8) or 70% (D7). (C) Group mean parameter values from the best-fit computational model of behavior (see text). Points indicate the mean of the posterior distribution of each parameter; error bars are 75% and 95% highest density intervals (HDIs). The computational model was fitted using data from discriminations (D5–D8) only. (D) The probability of “obeying” feedback, as for (B), but calculated using per-subject mean probabilities of “obeying” each kind of feedback, sampled from the best-fit computational model of behavior. The similarity to (B) indicates that the model successfully captured these aspects of behavior, even though the model incorporated no information about the “veracity” of preceding feedback. (E) Group mean differences in parameters from the best-fit computational model of behavior (see text), shown as the mean of the posterior distribution of each comparison parameter, directly sampled using Monte Carlo techniques from the hierarchical Bayesian inference model. Error bars are HDIs as before (orange, 75% HDI excludes zero; red, 95% HDI excludes zero). Percentages are the posterior probabilities that the parameter differs from 0 (width of the largest HDI excluding zero). The computational model was the same as that in (C).
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Related In: Results  -  Collection

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BHU102F3: Lowered 5-HT in the amygdala or OFC impaired probabilistic discrimination and reversal. (A) Number of errors prior to reaching criterion performance (excluding the day on which the criterion was passed), square-root transformed, for each stage. (B) The probability of “obeying” feedback from the preceding trial (i.e., of staying with the previously chosen stimulus following reward, or switching to the alternative stimulus following punishment). Data are from discrimination learning stages (D5–D8) only. The response to “true” (majority) or “false” (minority) feedback is shown separately; the proportion of majority feedback trials was 80% (D5, D6, D8) or 70% (D7). (C) Group mean parameter values from the best-fit computational model of behavior (see text). Points indicate the mean of the posterior distribution of each parameter; error bars are 75% and 95% highest density intervals (HDIs). The computational model was fitted using data from discriminations (D5–D8) only. (D) The probability of “obeying” feedback, as for (B), but calculated using per-subject mean probabilities of “obeying” each kind of feedback, sampled from the best-fit computational model of behavior. The similarity to (B) indicates that the model successfully captured these aspects of behavior, even though the model incorporated no information about the “veracity” of preceding feedback. (E) Group mean differences in parameters from the best-fit computational model of behavior (see text), shown as the mean of the posterior distribution of each comparison parameter, directly sampled using Monte Carlo techniques from the hierarchical Bayesian inference model. Error bars are HDIs as before (orange, 75% HDI excludes zero; red, 95% HDI excludes zero). Percentages are the posterior probabilities that the parameter differs from 0 (width of the largest HDI excluding zero). The computational model was the same as that in (C).
Mentions: Animals destined to receive either selective 5-HT depletions within the amygdala, OFC, or control surgery did not differ in their ability to learn a series of visual discriminations (one-way ANOVA errors to criterion, F < 1). Nor did they differ in their ability to remember a previously learned visual discrimination (one-way ANOVA errors to criterion, F < 1) postoperatively (mean errors to regain criterion, control 0.61 ± 0.6, 5-HT AMYG 1.8 ± 1.1, 5-HT OFC 0.6 ± 0.7). However, 5-HT depletions in either locus did significantly impair the acquisition and reversal of a series of novel discriminations, as assessed by the number of errors made before attaining criterion performance (Fig. 3A). The depleted groups did not differ from each other, and there was no interaction with discrimination/reversal stage. There were no differences between individual discriminations (despite some differences in reinforcement probability and the aversive outcome) or between individual reversals; unsurprisingly, more errors were made during reversals than during discrimination learning.Figure 3.

Bottom Line: To address this apparent discrepancy, the present study determined whether both effects could be found in the same animals by performing localized 5-HT depletions in the amygdala or orbitofrontal cortex (OFC) of a New World monkey, the common marmoset. 5-HT depletion in the amygdala impaired response choice on a probabilistic visual discrimination task by increasing the effectiveness of misleading, or false, punishment and reward, and decreased response suppression in a variable interval test of punishment sensitivity that employed the same reward and punisher. 5-HT depletion in the OFC also disrupted probabilistic discrimination learning and decreased response suppression.Computational modeling of behavior on the discrimination task showed that the lesions reduced reinforcement sensitivity.A novel, unitary account of the findings in terms of the causal role of 5-HT in the anticipation of both negative and positive motivational outcomes is proposed and discussed in relation to current theories of 5-HT function and our understanding of mood and anxiety disorders.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, University of Cambridge, Cambridge CB2 3EB, UK Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3EB, UK Current Address: Affective Cognitive Neuroscience Laboratory, Department of Behavioral Neurobiology and Drug Development, Institute of Pharmacology Polish Academy of Sciences, ul Smetna 12, 31-343 Krakow, Poland.

No MeSH data available.


Related in: MedlinePlus