Learning & memory最新文献

From early in life, we encounter both controllable environments, in which our actions can causally influence the reward outcomes we experience, and uncontrollable environments, in which they cannot. Environmental controllability is theoretically proposed to organize our behavior. In controllable contexts, we can learn to proactively select instrumental actions that bring about desired outcomes. In uncontrollable environments, Pavlovian learning enables hard-wired, reflexive reactions to anticipated, motivationally salient events, providing "default" behavioral responses. Previous studies characterizing the balance between Pavlovian and instrumental learning systems across development have yielded divergent findings, with some studies observing heightened expression of Pavlovian learning during adolescence and others observing a reduced influence of Pavlovian learning during this developmental stage. In this study, we aimed to investigate whether a theoretical model of controllability-dependent arbitration between learning systems might explain these seemingly divergent findings in the developmental literature, with the specific hypothesis that adolescents' action selection might be particularly sensitive to environmental controllability. To test this hypothesis, 90 participants, aged 8-27, performed a probabilistic-learning task that enables estimation of Pavlovian influence on instrumental learning, across both controllable and uncontrollable conditions. We fit participants' data with a reinforcement-learning model in which controllability inferences adaptively modulate the dominance of Pavlovian versus instrumental control. Relative to children and adults, adolescents exhibited greater flexibility in calibrating the expression of Pavlovian bias to the degree of environmental controllability. These findings suggest that sensitivity to environmental reward statistics that organize motivated behavior may be heightened during adolescence.

Memories of prior rewards bias our actions and future decisions. To determine the neural correlates of an appetitive associative learning task, we trained male mice to discriminate a reward-predicting cue over the course of 7 d. Encoding, recent recall, and remote recall were investigated to determine the areas of the brain recruited at each stage of learning. Using cFos as a proxy for neuronal activity, we found unique brain-wide patterns of activity across days that seem to correlate with distinct stages of learning. In particular, the prelimbic (PL) cortex was significantly recruited during the encoding of a novel association presentation, but its activity decreases as learning continues. To causally dissect the role of the PL in a reward memory across days, we chemogenetically inhibited first the PL entirely and then only tagged memory-bearing cells that were active during encoding in two stages of learning: early and late. Both nonspecific and specific PL inhibition experiments indicate that the PL drives behavior during late stages of learning to facilitate appropriate cue-driven behavior. Overall, our work underscores memory's role in discriminative reward seeking, and points to the PL as a target for modulating disorders in which impaired reward processing is a core component.

The odor span task (OST) infers working memory capacity (WMC) by requiring rodents to discriminate between previously presented and session-novel odors to obtain a hidden food reward. Here, rats' responses to session-novel odors and food rewards were assessed to determine whether rats use mitigating strategies in the OST. Rats accurately responded to session-novel odors but also reliably responded to the food reward alone and performed at chance when both a session-novel odor and food reward were presented in separate locations. The inclusion of unscented sand in the cups holding the food reward significantly reduced the rats' responses to the food reward alone. Collectively, these results demonstrate the need for rigorous tests of potential mitigating strategies and hold wide implications for rodent odor discrimination-based behavioral tasks.

We investigated whether retrograde amnesia for the stress-induced impairment of extinction retrieval shares similar characteristics with original acquisition memories. The first experiment demonstrated that cycloheximide administered shortly after a single restraint stress session alleviated the impairment of extinction retrieval but not when administered following a longer delay (i.e., the amnesia for stress is time-dependent). A second experiment showed that the retrograde amnesia for stress could be alleviated by a second brief exposure to the stressor. These results demonstrating that amnesia for stress shares characteristics similar to original memories are explained using a retrieval-based memory integration model of retrograde amnesia.

Memory retrieval is strikingly susceptible to external states (environment) and internal states (mood states and alcohol), yet we know little about the underlying mechanisms. We examined how internally generated states influence successful memory retrieval using the functional magnetic resonance imaging (fMRI) of laboratory mice during memory retrieval. Mice exhibited a strong tendency to perform memory retrieval correctly only in the reinstated mammillary body-inhibited state, in which mice were trained to discriminate auditory stimuli in go/no-go tasks. fMRI revealed that distinct auditory cues engaged differential brain regions, which were primed by internal state. Specifically, a cue associated with a reward activated the lateral amygdala, while a cue signaling no reward predominantly activated the postsubiculum. Modifying these internal states significantly altered the neural activity balance between these regions. Optogenetic inhibition of those regions in the precue period blocked the retrieval of type-specific memories. Our findings suggest that memory retrieval is under the control of two interrelated neural circuits underlying the neural basis of state-dependent memory retrieval.

There is debate as to whether a time-dependent transformation of the episodic-like memory network is observed for nonepisodic tasks, including procedural motor memory. To determine how motor memory networks reorganize with time and practice, mice performed a motor task in a straight alley maze for 1 d (recent), 20 d of continuous training (continuous), or testing 20 d after the original training (remote), and then regional c-Fos expression was assessed. Elevated hippocampal c-Fos accompanied remote, but not continuous, motor task retrieval after 20 d, suggesting that the hippocampus remains engaged for nonhabitual remote motor memory retrieval.

Male and female 3xTg-AD mice between 5 and 24 mo of age and their B6129F2/J wild-type controls were tested on a series of 18 olfactory discrimination and reversal tasks in an operant olfactometer. All mice learned the odor discriminations and reversals to a criterion of 85% correct, but the 3xTg-AD mice made fewer errors than the B6129F2/J mice in the odor discriminations and in the first six reversal learning tasks. Many mice showed evidence of near errorless learning, and on the reversal tasks the 3xTg-AD mice showed more instances of near errorless learning than the B6129F2/J mice. There was no evidence of an age effect on odor discrimination, but there was a decrease in errorless reversal learning in aged B6129F2/J mice. In long-term memory tests, there was an increase in the number of errors made but no genotype difference. The high level of performance indicates that the mice were able to develop a "learning to learn" strategy. The finding that the 3xTg-AD mice outperformed their littermate controls provides an example of paradoxical functional facilitation in these mice.