Considerable evidence implicates the basolateral amygdala (BLA) in the formation of outcome representations that link cues to the incentive properties of reinforcers. Animals with BLA damage show impaired performance in reinforcer devaluation tasks, in which the value of the food reinforcer is reduced by satiation or food-toxin pairings after the completion of cue or response training. Although intact animals spontaneously reduce their conditioned responding after such reinforcer devaluation procedures, animals with BLA lesions made before training typically do not, as evidenced across a range of species, training contingencies and devaluation procedures. By contrast, the role of the BLA in devaluation task performance once such outcome representations are established is unclear. Whereas Pickens et al. (2003) found normal devaluation performance in rats when BLA lesions were made after Pavlovian light→food pairings but before devaluation by food-toxin pairings, Ostlund and Balleine (2008) found impaired devaluation performance when BLA lesions were made after instrumental training with multiple instrumental responses and food reinforcers, but before devaluation of one reinforcer by selective satiation. Those studies differed in their use of Pavlovian or operant training contingencies, single or multiple reinforcers, and associative or motivational devaluation procedures. Here we found that when multiple reinforcers were used, post-training BLA lesions disrupted the expression of devaluation performance in rats, using either Pavlovian or instrumental training procedures, and either conditioned taste aversion or satiation devaluation procedures. Thus, BLA apparently plays a critical role in maintaining or using sensory associations of reinforcer value when multiple outcomes must be coded, but not under single-outcome conditions.

The AMPA receptor subunit glutamate receptor 1 (GluR1 or GluR-A) contributes to amygdala-dependent emotional learning. It remains unclear, however, to what extent different amygdala pathways depend on GluR1, or other AMPA receptor subunits, for proper synaptic transmission and plasticity, and whether GluR1-dependent long-term potentiation (LTP) is necessary for auditory and contextual fear conditioning. Here, we dissected the role of GluR1 and GluR3 (GluR-C) subunits in AMPA receptor-dependent amygdala LTP and fear conditioning using knock-out mice (GluR1 Ϫ/Ϫ and GluR3 Ϫ/Ϫ ). We found that, whereas LTP at thalamic inputs to lateral amygdala (LA) projection neurons and at glutamatergic synapses in the basal amygdala was completely absent in GluR1 Ϫ/Ϫ mice, both GluR1 and GluR3 contributed to LTP in the cortico-LA pathway. Because both auditory and contextual fear conditioning were selectively impaired in GluR1 Ϫ/Ϫ but not GluR3 Ϫ/Ϫ mice, we conclude that GluR1-dependent synaptic plasticity is the dominant form of LTP underlying the acquisition of auditory and contextual fear conditioning, and that plasticity in distinct amygdala pathways differentially contributes to aversive conditioning.

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Guided by features of molecular, cellular, and circuit dysfunction affecting the prefrontal cortex in clinical investigations, we targeted prefrontal cortex in studies of a model for neuropsychiatric illness using transgenic mice expressing a putative dominantnegative disrupted in schizophrenia 1 (DN-DISC1). We detected marked augmentation of GAPDH-seven in absentia homolog Siah protein binding in the DISC1 mice, a major hallmark of a nuclear GAPDH cascade that is activated in response to oxidative stress. Furthermore, deficits were observed in well-defined tests for the cognitive control of adaptive behavior using reversal learning and reinforcer devaluation paradigms. These deficits occurred even though DN-DISC1 mice showed intact performance in simple associative learning and normal responses in consumption of reward. In an additional series of assessments, motivational functions also were impoverished in DN-DISC1 mice, including tests of the dynamic modulation of reward value by effortful action, progressive ratio performance, and social behavior. Augmentation of an oxidative stress-associated cascade (e.g., a nuclear GAPDH cascade) points to an underlying condition that may contribute to the profile of cognitive and motivational impairments in DN-DISC1 mice by affecting the functional integrity of the prefrontal cortex and dysfunction within its connected networks. As such, this model should be useful for further preclinical research and drug discovery efforts relevant to the burden of prefrontal dysfunction in neuropsychiatric illness.cognition | depression | orbitofrontal cortex I t has long been noted that the cognitive impairments in patients with major mental illness, such as schizophrenia and mood disorders, point to dysfunction of the frontal lobe (1-3). More recent translational studies based on cognitive and affective neuroscience approaches suggest the associated deficits in neuropsychiatric populations reflect abnormal functioning of prefrontal-subcortical circuitry responsible for cognitive and emotional control (4-7). By examining disorders of brain circuitry, these studies offer the potential to advance therapeutic treatment (7,8).The impaired integrity affecting prefrontal circuitry in schizophrenia and mood disorders in part reflects neuropathology associated with decreased parvalbumin immunoreactivity (9-11), a marker for fast-spiking inhibitory interneurons, which are critical for cognitive function (9, 10). One possible cause of impaired integrity affecting that interneuron population comes from evidence that decreased parvalbumin immunoreactivity is elicited by oxidative stress in mouse models relevant to neuropsychiatric illness (12-15). Oxidative stress can be driven by a deficiency in antioxidant defenses, which leads to increased oxidative signaling resulting in damage to DNA, proteins, and fatty acids (16). Central nervous system cells are particularly vulnerable to these effects because of reduced antioxidant levels and elevated metabolic rate (13).Genetic studies also are contribu...

In reinforcer-selective transfer, Pavlovian stimuli that are predictive of specific outcomes bias performance toward responses associated with those outcomes. Although this phenomenon has been extensively examined in rodents, recent assessments have extended to humans. Using a stock market paradigm adults were trained to associate particular symbols and responses with particular currencies. During the first test, individuals showed a preference for responding on actions associated with the same outcome as that predicted by the presented stimulus (i.e., a reinforcer-selective transfer effect). In the second test of the experiment, one of the currencies was devalued. We found it notable that this served to reduce responses to those stimuli associated with the devalued currency. This finding is in contrast to that typically observed in rodent studies, and suggests that participants in this task represented the sensory features that differentiate the reinforcers and their value during reinforcer-selective transfer. These results are discussed in terms of implications for understanding associative learning processes in humans and the ability of reward-paired cues to direct adaptive and maladaptive behavior.