Comparative evidence for the importance of the amygdala in regulating reward salience

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Highlights

  • Amygdala responds to stimuli of positive (reward) and negative (aversive) valence.

  • Reduced reward salience is a major and trans-diagnostic psychopathology.

  • Stress-induced amygdala changes could mediate reduced reward salience.

  • Amygdala reward neurons constitute a potential target for restoring reward salience.

Environmental stimuli and life events are often of emotional relevance to the individual. This is due to their recognition and processing by the brain's neural circuits for emotion. In terms of emotion valence, stimuli/events can be neutral (non-emotional), rewarding or aversive. In addition to its basic valence, the salience of an emotional stimulus, that is, how rewarding or how aversive it is, is also of critical importance. Quantitative changes in stimulus reward salience or aversion salience are likely to underlie some major symptoms in stress-related mental disorders. This includes low reward salience as the basis for diminished interest or pleasure in major depressive disorder (MDD) and for apathy (negative symptoms) in schizophrenia, and high aversion salience as the basis for depressed mood in MDD. Insight into the brain region(s) and cellular microcircuits wherein the saliences of reward and aversion stimuli are set is essential for understanding the neurobiology of emotion in health and mental disorders. Here I review the current evidence for the role of the amygdala in processing reward valence and salience, based on studies conducted in human, monkey and, in particular, rat and mouse. Human BOLD-fMRI studies demonstrate amygdala reactivity to reward and its reduction in MDD and schizophrenia. In monkey, some neurons in the basolateral amygdala (BLA) are responsive to reward, aversion, or both. In rat, BLA reward neurons regulate excitation of nucleus accumbens (NAcc) neurons, whereas chronic stress increases intra-amygdala synaptic activity. In mouse, there are BLA glutamatergic principal reward neurons and aversion neurons. Based on this comparative evidence, this review concludes that the mammalian BLA reward neurons could constitute a major contributor to the neural circuitry of reward salience and a critical node in reward pathology.

Section snippets

Amygdala anatomy and aversion processing

The amygdala is located in the temporal lobe and comprises a complex of subcortical nuclei. In knowledge obtained primarily from rodent studies, it is a major brain region in the neural circuitry of emotion in terms of: inputs received from sensory regions, for example, sensory thalamus, sensory cortex; cellular and microcircuit responding to innate emotional stimuli; learning about and storing memories for the association between neutral to-be-conditioned stimuli and innate emotional stimuli;

Human amygdala for reward processing and in emotional disorder

In human and rodent research, the contribution of the ventral tegmental area-nucleus accumbens (VTA-NAcc) dopaminergic mesolimbic pathway to reward processing [10, 11] and the contribution of the amygdala to aversion processing ([12]; see previous section), have both received considerable scientific attention. It is only relatively recently that the emphasis has started to shift towards recognizing that each of these (and other) brain regions is essential for both reward and aversion

Amygdala for reward including dedicated reward neurons

As in the human case, the small number of rodent studies of amygdala reward processing has yielded affirmative data [19]. For example, in rats it was demonstrated that LA lesion attenuated amphetamine-induced conditioned place preference [20]. Also in rats, subjects underwent sham-lesion or BLA-lesion and were then trained on an operant response-reward contingency and a stimulus-reward Pavlovian contingency, where reward was sweet food. In subsequent tests, BLA-lesioned rats exhibited

Basolateral amygdala reward neurons and the processing of reward salience

Therefore, whilst the critical details of the micro-circuitry of the BLA reward neurons and aversion neurons in terms of topography and projection regions is currently debated, the comparative evidence for existence of exclusively reward-sensitive and exclusively aversion-sensitive BLA neurons is conclusive (Figure 1a). With regards to function these neurons are stated to be emotion-valence specific. It can be hypothesized that in addition to this, within the emotion valence to which they are

Stress, amygdala and reward salience

Chronic exposure of animals to stress in the form of uncontrollable and/or unpredictable aversive stimuli allows for the study of its effects on amygdala function and could well provide important insights into amygdala pathophysiology in emotional disorders. Whilst chronic stress has been demonstrated to induce increased sensitivity to aversion in amygdala-dependent behavioural paradigms, for example, Pavlovian fear conditioning [29] and decreased sensitivity to reward [30, 31, 32], there have

Conclusions

There has been a relative lack of progress in discovering much-needed novel molecular targets and developing more effective treatments for stress-related mental disorders. To a large extent, paucity of knowledge of the neural circuitry underlying major psychological processes accounts for this lack of progress. In particular, this concerns the cellular and molecular changes in specific brain regions impacted by environmental and epigenetic aetiological factors that constitute the

Conflicts of interest statement

Nothing declared.

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgements

This review was supported by a grant from the Swiss National Science Foundation (31003A-160147).

References (37)

  • C. Herry et al.

    Switching on and off fear by distinct neuronal circuits

    Nature

    (2008)
  • J. Kim et al.

    Basolateral to central amygdala neural circuits for appetitive behaviors

    Neuron

    (2017)
  • J. Kim et al.

    Antagonistic negative and positive neurons of the basolateral amygdala

    Nat Neurosci

    (2016)
  • A. Vazdarjanova et al.

    Basolateral amygdala is not critical for cognitive memory of contextual fear conditioning

    Proc Natl Acad Sci U S A

    (1998)
  • S. Maren et al.

    The contextual brain: implications for fear conditioning, extinction and psychopathology

    Nat Rev Neurosci

    (2013)
  • D.A. Pizzagalli

    Depression, stress, and anhedonia: toward a synthesis and integrated model

    Annu Rev Clin Psychol

    (2014)
  • S.R. Sesack et al.

    Cortico-basal ganglia reward network: microcircuitry

    Neuropsychopharmacology

    (2010)
  • S.G. Disner et al.

    Neural mechanisms of the cognitive model of depression

    Nat Rev Neurosci

    (2011)
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