Visual stimuli can acquire positive or negative value through their association with rewards and punishments, a process called reinforcement learning. Although we now know a great deal about how the brain analyses visual information, we know little about how visual representations become linked with values. To study this process, we turned to the amygdala, a brain structure implicated in reinforcement learning 1-5 . We recorded the activity of individual amygdala neurons in monkeys while abstract images acquired either positive or negative value through conditioning. After monkeys had learned the initial associations, we reversed image value assignments. We examined neural responses in relation to these reversals in order to estimate the relative contribution to neural activity of the sensory properties of images and their conditioned values. Here we show that changes in the values of images modulate neural activity, and that this modulation occurs rapidly enough to account for, and correlates with, monkeys' learning. Furthermore, distinct populations of neurons encode the positive and negative values of visual stimuli. Behavioural and physiological responses to visual stimuli may therefore be based in part on the plastic representation of value provided by the amygdala.The complex anatomical connections of the amygdala, a collection of nuclei located deep in the medial temporal lobe, make it a prime candidate for providing a representation of the value of visual stimuli. The amygdala receives inputs from the visual system and from other sensory systems that represent reinforcing stimuli 6-8 . In addition, the amygdala is likely to receive error signals that represent stimuli in relation to expectations and that may be essential in creating an updated representation of value. The source of error signals for aversive learning has not been identified; however, midbrain dopamine neurons might supply such error signals for appetitive learning 9 . These signals could influence amygdala neural responses either directly 7 or indirectly through other brain structures such as the prefrontal cortex 6,10 . The convergence of information from each of these input pathways, perhaps combined with processing that occurs through intrinsic connections within the amygdala, may form a representation of visual stimulus value.Correspondence and requests for materials should be addressed to C.D.S. (cds2005@columbia.edu). * These authors contributed equally to this work.Author Contributions J.J.P. and M.A.B. performed all experiments and conducted data analyses. S.E.M. performed some of the data analyses and contributed to many discussions. Experiments were designed and implemented in the laboratory of C.D.S. Unlike the anatomy of the amygdala, the physiological properties of amygdala neuronsespecially with respect to learning the value of visual stimuli-remain poorly understood. We therefore recorded the activity of single amygdala neurons while monkeys learned the positive or negative value of new, abstract images during a tr...

Animals and humans learn to approach and acquire pleasant stimuli and to avoid or defend against aversive ones. However, both pleasant and aversive stimuli can elicit arousal and attention, and their salience or intensity increases when they occur by surprise. Thus, adaptive behavior may require that neural circuits compute both stimulus valence--or value--and intensity. To explore how these computations may be implemented, we examined neural responses in the primate amygdala to unexpected reinforcement during learning. Many amygdala neurons responded differently to reinforcement depending upon whether or not it was expected. In some neurons, this modulation occurred only for rewards or aversive stimuli, but not both. In other neurons, expectation similarly modulated responses to both rewards and punishments. These different neuronal populations may subserve two sorts of processes mediated by the amygdala: those activated by surprising reinforcements of both valences-such as enhanced arousal and attention-and those that are valence-specific, such as fear or reward-seeking behavior.

Summary Recent advances indicate that the amygdala represents valence: a general appetitive/aversive affective characteristic that bears similarity to the neuroeconomic concept of value. Neurophysiological studies show that individual amygdala neurons respond differentially to a range of stimuli with positive or negative affective significance. Meanwhile, increasingly specific lesion/inactivation studies reveal that the amygdala is necessary for processes – e.g., fear extinction and reinforcer devaluation – that involve updating representations of value. Furthermore, recent neuroimaging studies suggest that the human amygdala mediates performance on many reward-based decision-making tasks. The encoding of affective significance by the amygdala might be best described as a representation of state value – a representation that is useful for coordinating physiological, behavioral, and cognitive responses in an affective/emotional context.

Neuroscientists, psychologists, clinicians, and economists have long been interested in how individuals weigh information about potential rewarding and aversive stimuli to make decisions and to regulate their emotions. However, we know relatively little about how appetitive and aversive systems interact in the brain, as most prior studies have investigated only one valence of reinforcement. Previous work has suggested that primate orbitofrontal cortex (OFC) represents information about the reward value of stimuli. We therefore investigated whether OFC also represents information about aversive stimuli, and, if so, whether individual neurons process information about both rewarding and aversive stimuli. Monkeys performed a trace conditioning task in which different novel abstract visual stimuli (conditioned stimuli, CSs) predicted the occurrence of one of three unconditioned stimuli (USs): a large liquid reward, a small liquid reward, or an aversive air-puff. Three lines of evidence suggest that information about rewarding and aversive stimuli converges in individual neurons in OFC. First, OFC neurons often responded to both rewarding and aversive USs, despite their different sensory features. Second, OFC neural responses to CSs often encoded information about both potential rewarding and aversive stimuli, even though these stimuli differed in both valence and sensory modality. Finally, OFC neural responses were correlated with monkeys' behavioral use of information about both rewarding and aversive CS-US associations. These data indicate that processing of appetitive and aversive stimuli converges at the single cell level in OFC, providing a possible substrate for executive and emotional processes that require using information from both appetitive and aversive systems.

Gramicidin A (gA), with four Trp residues per monomer, has an increased conductance compared to its Phe replacement analogs. When the dipole moment of the Trp13 side chain is increased by fluorination at indole position 5 (FgA), the conductance is expected to increase further. gA and FgA conductances to Na+, K+, and H+ were measured in planar diphytanoylphosphatidylcholine (DPhPC) or glycerylmonoolein (GMO) bilayers. In DPhPC bilayers, Na+ and K+ conductances increased upon fluorination, whereas in GMO they decreased. The low ratio in the monoglyceride bilayer was not reversed in GMO-ether bilayers, solvent-inflated or -deflated bilayers, or variable fatty acid chain monoglyceride bilayers. In both GMO and DPhPC bilayers, fluorination decreased conductance to H+ but increased conductance in the mixed solution, 1 M KCl at pH 2.0, where K+ dominates conduction. Eadie-Hofstee plot slopes suggest similar destabilization of K+ binding in both lipids. Channel lifetimes were not affected by fluorination in either lipid. These observations indicate that fluorination does not change the rotameric conformation of the side chain. The expected difference in the rate-limiting step for transport through channels in the two bilayers qualitatively explains all of the above trends.