Within most contemporary learning theories, reinforcement prediction error, the difference between the obtained and expected reinforcer value, critically influences associative learning. In some theories, this prediction error determines the momentary effectiveness of the reinforcer itself, such that the same physical event produces more learning when its presentation is surprising than when it is expected. In other theories, prediction error enhances attention to potential cues for that reinforcer by adjusting cue-specific associability parameters, biasing the processing of those stimuli so that they more readily enter into new associations in the future. A unique feature of these latter theories is that such alterations in stimulus associability must be represented in memory in an enduring fashion. Indeed, considerable data indicate that altered associability may be expressed days after its induction. Previous research from our laboratory identified brain circuit elements critical to the enhancement of stimulus associability by the omission of an expected event, and to the subsequent expression of that altered associability in more rapid learning. Here, for the first time, we identified a brain region, the posterior parietal cortex, as a potential site for a memorial representation of altered stimulus associability. In three experiments using rats and a serial prediction task, we found that intact posterior parietal cortex function was essential during the encoding, consolidation, and retrieval of an associability memory enhanced by surprising omissions. We discuss these new results in the context of our previous findings and additional plausible frontoparietal and subcortical networks.

Rats will approach and contact a lever whose insertion into the chamber signals response-independent food delivery. This “autoshaping” or “sign-tracking” phenomenon has recently attracted considerable attention as a platform for studying individual differences in impulsivity, drug sensitization, and other traits associated with vulnerability to drug addiction. Here we examined two basic stimulus selection phenomena, blocking and overshadowing, in the autoshaped lever-pressing of rats. Blocking and overshadowing were decidedly asymmetrical. Previously reinforced lever-extension conditioned stimuli (CSs) completely blocked conditioning to auditory cues (Experiments 1 and 2), and previously nonreinforced lever-extension CSs overshadowed conditioning to auditory cues. By contrast, conditioning to lever-extension CSs was not blocked by either auditory (Experiment 3) or lever insertion (Experiment 4) cues, and was not overshadowed by auditory cues. Conditioning to a lever insertion cue was somewhat overshadowed by the presence of another lever, especially in terms of food cup behavior displayed after lever withdrawal. We discussed several frameworks in which the apparent immunity of autoshaped lever-pressing to blocking might be understood. Given evidence that different brain systems are engaged when different kinds of cues are paired with food delivery, it is worth considering the possibility that interactions among them in learning and performance may follow different rules. In particular, it is intriguing to speculate that the roles of simple cue-reinforcer contiguity as well as of individual and aggregate reinforcer prediction errors may differ across stimulus classes.

Whether synthetic genomes can power life has attracted broad interest in the synthetic biology field, especially when the synthetic genomes are extensively modified with thousands of designer features. Here we report de novo synthesis of the largest eukaryotic chromosome thus far, synIV, a 1,454,621-bp Saccharomyces cerevisiae chromosome resulting from extensive genome streamlining and modification. During the construction of synIV, we developed a megachunk assembly method, combined with a hierarchical integration strategy. This strategy significantly increased the accuracy and flexibility of synthetic chromosome construction and facilitated chromosome debugging. In addition to the drastic sequence changes made to synIV by rewriting it, we further manipulated the three-dimensional structure of synIV in the yeast nucleus to explore spatial gene regulation within the nuclear space. Surprisingly, we found few gene expression changes, suggesting that positioning inside the yeast nucleoplasm plays a minor role in gene regulation. Therefore, our manipulation of the spatial structure of the largest synthetic yeast chromosome shed light on higher-order architectural design of the synthetic genomes.