Temporal prediction error triggers amygdala-dependent memory updating in appetitive operant conditioning in rats.

Reinforcement learning theories postulate that prediction error, i.e., a discrepancy between the actual and expected outcomes, drives reconsolidation and new learning, inducing an updating of the initial memory. Pavlovian studies have shown that prediction error detection is a fundamental mechanism in triggering amygdala-dependent memory updating, where the temporal relationship between stimuli plays a critical role. However, in contrast to the well-established findings in aversive situations (e.g., fear conditioning), only few studies exist on prediction error in appetitive operant conditioning, and even less with regard to the role of temporal parameters. To explore if temporal prediction error in an appetitive operant paradigm could generate an updating and consequent reconsolidation and/or new learning of temporal association, we ran four experiments in adult male rats. Experiment 1 verified whether an unexpected delay in the time of reward's availability (i.e., a negative temporal prediction error) in a single session produces an updating in long-term memory of temporal expectancy in an appetitive operant conditioning. Experiment 2 showed that negative prediction errors, either due to the temporal change or through reward omission, increased in the basolateral amygdala nucleus (BLA) the activation of a protein that is critical for memory formation. Experiment 3 revealed that the presence of a protein synthesis inhibitor (anisomycin) in the BLA during the session when the reward was delayed (Error session) affected the temporal updating. Finally, Experiment 4 showed that anisomycin, when infused immediately after the Error session, interfered with the long-term memory of the temporal updating. Together, our study demonstrated an involvement of BLA after a change in temporal and reward contingencies, and in the resulting updating in long-term memory in appetitive operant conditioning.

Updating temporal expectancy of an aversive event engages striatal plasticity under amygdala control.

Pavlovian aversive conditioning requires learning of the association between a conditioned stimulus (CS) and an unconditioned, aversive stimulus (US) but also involves encoding the time interval between the two stimuli. The neurobiological bases of this time interval learning are unknown. Here, we show that in rats, the dorsal striatum and basal amygdala belong to a common functional network underlying temporal expectancy and learning of a CS-US interval. Importantly, changes in coherence between striatum and amygdala local field potentials (LFPs) were found to couple these structures during interval estimation within the lower range of the theta rhythm (3-6 Hz). Strikingly, we also show that a change to the CS-US time interval results in long-term changes in cortico-striatal synaptic efficacy under the control of the amygdala. Collectively, this study reveals physiological correlates of plasticity mechanisms of interval timing that take place in the striatum and are regulated by the amygdala.

Role of the amygdala in the reinforcement omission effect

The reinforcement omission effect (ROE) has been attributed to both motivational and attentional consequences of surprising reinforcement omission. Recent evidence suggests that the basolateral complex of the amygdala is involved in motivational components related to reinforcement value, whereas the central nucleus of the amygdala is involved in the processing of the attentional consequences of surprise. This study was designed to verify whether the mechanisms involved in the ROE depend on the integrity of either the basolateral amygdala complex or central nucleus of the amygdala. The ROE was evaluated in rats with lesions of either the central nucleus or basolateral complex of the amygdala and trained on a fixed-interval schedule procedure (Experiment 1) and fixed-interval with limited hold signaled schedule procedure (Experiment 2). The results of Experiment 1 showed that sham-operated rats and rats with lesions of either the central nucleus or basolateral area displayed the ROE. In contrast, in Experiment 2, subjects with lesions of the central nucleus or basolateral complex of the amygdala exhibited a smaller ROE compared with sham-operated subjects. Thus, the effects of selective lesions of amygdala subregions on the ROE in rats depended on the training procedure. Furthermore, the absence of differences between the lesioned groups in either experiment did not allow the dissociation of attentional or motivational components of the ROE with functions of specific areas of the amygdala. Thus, results did not show a functional double-dissociation between the central nucleus and basolateral area in the ROE.(AU)

Role of the amygdala in the reinforcement omission effect

The reinforcement omission effect (ROE) has been attributed to both motivational and attentional consequences of surprising reinforcement omission. Recent evidence suggests that the basolateral complex of the amygdala is involved in motivational components related to reinforcement value, whereas the central nucleus of the amygdala is involved in the processing of the attentional consequences of surprise. This study was designed to verify whether the mechanisms involved in the ROE depend on the integrity of either the basolateral amygdala complex or central nucleus of the amygdala. The ROE was evaluated in rats with lesions of either the central nucleus or basolateral complex of the amygdala and trained on a fixed-interval schedule procedure (Experiment 1) and fixed-interval with limited hold signaled schedule procedure (Experiment 2). The results of Experiment 1 showed that sham-operated rats and rats with lesions of either the central nucleus or basolateral area displayed the ROE. In contrast, in Experiment 2, subjects with lesions of the central nucleus or basolateral complex of the amygdala exhibited a smaller ROE compared with sham-operated subjects. Thus, the effects of selective lesions of amygdala subregions on the ROE in rats depended on the training procedure. Furthermore, the absence of differences between the lesioned groups in either experiment did not allow the dissociation of attentional or motivational components of the ROE with functions of specific areas of the amygdala. Thus, results did not show a functional double-dissociation between the central nucleus and basolateral area in the ROE.

Efeitos da omissão de reforço em ratos com lesões do núcleo central e complexo basolateral da amígdala

Os efeitos de omissão do reforço (EORs) são caracterizados por taxas de respostas mais altas após a omissão do que após a libera,cão do reforço. Este padrão de comportamento é interpretado em termos de processamentos motivacionais e atencionais. A amígdala tem sido implicada numa variedade de funções motivacionais e atencionais relacionadas à aprendizagem apetitiva e aversiva Estudos mais antigos mostraram que lesões eletrolíticas do complexo amidalóide prejudicaram os EORs. Entretanto, trabalhos mais recentes utilizando lesões neurotóxicas amplas da amígdala, porém mais seletivas, não encontraram os mesmos resultados ao verificar o efeito de redução do reforço. Alguns estudos que verificaram os EORs ou o efeito de redução do reforço, em ratos com lesões bilaterais do núcleo central da amígdala (CN) ou em ratos com lesões bilaterais do complexo basolateral da amígdala (BLA), encontram resultados divergentes. Além disso, outro estudo sugere uma lateralização entre o hemisfério esquerdo e direito da amígdala em relação ao efeito da redução do reforço. Assim, o presente estudo verificou se o comprometimento funcional ligado à ativação ampla ou seletiva da amígdala afeta os EORs. No Experimento 1, os animais foram submetidos à lesão neurotóxica bilateral ampla da amígdala, envolvendo o CN e o BLA....(AU)

Reinforcement omission effects (ROEs) are characterized by higher response rates after the reinforcement omission than after its delivery. This pattern of behavior is interpreted in terms of motivational and attentional processes. The amygdala has been implicated in a variety of motivational and attentional functions related to appetitive and aversive learning. Older studies showed that electrolytic lesions of the amygdaloid complex disrupted the EORs. However, recent studies did not find the same results to verify the reward reduction effect in rats with neurotoxic lesions of the amygdala. Furthermore, some studies found conflicting results when examined the ROEs and reward reduction effect in rats with bilateral lesions of the central nucleus of the amygdala (CN) or in rats with bilateral lesions of the basolateral complex of the amygdala (BLA). Moreover, another study suggests a lateralization of amygdala involvement in reward reduction. Thus, this study examined if the functional impairment related to broad or selective activation of the amygdala interferes with ROEs. In Experiment 1, rats were submitted to bilateral neurotoxic lesions of the amygdala, involving the CN and BLA. ...(AU)

Influence of the reinforcement magnitude on omission effects.

Reinforcement Omission Effects (ROEs), indicated by higher rate of responses after nonreinforced trials in a partial reinforcement schedule, have been interpreted as behavioral transient facilitation after nonreinforcement induced by primary frustration, and/or behavioral transient inhibition after reinforcement induced by demotivation or temporal control. The size of the ROEs should depend directly on the reinforcement magnitude. The present experiment aimed to clarify the relationship between reinforcement magnitude and the omission effects manipulating the magnitude linked to discriminative stimuli in a partial reinforcement FI schedule. The results showed that response rates were higher after omission than after reinforcement delivery. Besides, response rates were highest immediately after the reinforcement omission of a larger magnitude than of a smaller magnitude. These data are interpreted in terms of ROEs multiple process behavioral facilitation after nonreinforcement, and behavioral transient inhibition after reinforcement.