Neurobiology of Learning and Memory最新文献

Predicting when future events will occur is critical for adaptive behavior, yet the brain networks underlying this ability remain unclear. The prefrontal cortex (PFC) and its rodent analogue, the prelimbic cortex (PL), are known to support the ability to track time and execute decisions in anticipation of upcoming events. Given this, we can expand our understanding of the circuits involved in time-based behavior by looking for regions that interact with the PFC during timing tasks. The mediodorsal nucleus of the thalamus (MD) is a strong candidate, as it shares dense reciprocal connections with the PFC and is widely implicated in higher-order cognition. However, data implicating the. MD itself in timing is still minimal, and to our knowledge, causal data directly implicating MD-PFC communication in timing is lacking entirely. To address this, we trained nineteen male Long Evans rats on a dual interval timing task requiring decision-making and tested the effects of reversibly inactivating the MD/PL individually or blocking communication between them using GABA-A receptor agonist, muscimol. All manipulations produced a similar deficit-flattening the characteristic Gaussian-shaped reponse curves while leaving overall response rates intact. Single-trial analyses revealed that this was not simply a broadening of temporally-controlled response bursts, but rather a fundatment breakedown in the canonical burst structure of timing behavior, with responses becoming more uniflormly distrubted across the trial. These findings further implicate the MD and PL in timing and, to our knowledge, provide the first causal evidence that communication between the MD and PFC is specifically required. More broadly, these findings add to growing evidence that MD-PFC interactions support higher-order cognition. Timing impairments are common in a variety of neuropsychiatric diseases including schizophrenia, Parkinson's disease, autism, and bipolar disorder so this work provides key implications for the involvement of a novel MD-PFC pathway.

Forming pavlovian associations is fundamental to human behaviour. From gambling to social interactions, rewards are frequently preceded by motor actions. While studies have shown that making a choice enhances reward learning, in many cases (e.g. playing a slot machine), actions are performed without control over outcomes. We investigated the impact of performing an action on reward processing and associative learning in the absence of choice. We used a task in which coloured houses were probabilistically associated with social reward or punishment. On a trial-wise basis, we randomised whether participants pressed a button prior to observing the outcome, or waited passively. Using fMRI we explored the impact of performing an action on reward processing. Contrary to our hypotheses, we did not find reward-related activity in the striatum, nor a modulation of striatal activity by performing an action. Instead, we found tentative evidence for enhanced reactivity to negative outcomes in active trials in areas associated with affective processing and memory formation. Cues predicting positive outcomes were associated with enhanced activity in the temporo-parietal junction and precuneus. In a second, behavioral study, we used a forced-choice task testing the formation of stimulus-outcome associations. Participants preferred stimuli associated with reward over those associated with punishment. Both approach and avoidance were enhanced for stimuli learned in active trials. These findings suggest that performing a motor action enhances pavlovian-type associative learning, and may facilitate the neural processing of outcomes. This has important implications for our understanding of human learning, as well as gambling and other reward-driven behaviours.

We often choose to learn motor skills not only because of some external reward, but also because motor learning, in and of itself, is satisfying. While dopamine is thought to drive reward-based motor learning, it remains unclear whether dopamine is implicated in motor learning under conditions ostensibly driven by intrinsic rewards/motivation (i.e., in the absence of extrinsic feedback or reward). Here, by pharmacologically manipulating dopamine using the dopamine precursor Levodopa, we investigated the role of dopamine in an explicit motor learning task guided by internally determined signals of performance success, by removing intrinsic feedback about task success. Specifically, we asked participants to strategically aim away from presented targets by various instructed angles: a form of explicit motor learning that contributes to performance in the classic visuomotor rotation task. In the feedback condition, targets jumped mid-movement by the instructed angle, such that success in target hitting depended on successfully aiming away by the instructed angle. In the no-feedback condition, intrinsic feedback about task success was removed by having targets disappear mid-movement, such that participants could not know if they succeeded at hitting the targets or not. We found that dopamine altered performance, both with and without task feedback about task success. This provides direct evidence for a role of dopamine in motor learning driven by internal task goals.