Inhibitory interneurons are thought to play crucial roles in diverse brain functions. However, roles of different inhibitory interneuron subtypes in working memory remain unclear. We found distinct activity patterns and stimulation effects of two major interneuron subtypes, parvalbumin (PV)- and somatostatin (SOM)-expressing interneurons, in the medial prefrontal cortex of mice performing a spatial working memory task. PV interneurons showed weak target-dependent delay-period activity and were strongly inhibited by reward. By contrast, SOM interneurons showed strong target-dependent delay-period activity, and only a subtype of them was inhibited by reward. Furthermore, optogenetic stimulation of PV and SOM interneurons preferentially suppressed discharges of putative pyramidal cells and interneurons, respectively. These results indicate different contributions of PV and SOM interneurons to prefrontal cortical circuit dynamics underlying working memory.

Learning to predict rewards based on environmental cues is essential for survival. It is believed that animals learn to predict rewards by updating predictions whenever the outcome deviates from expectations, and that such reward prediction errors (RPEs) are signaled by the mesolimbic dopamine system—a key controller of learning. However, instead of learning prospective predictions from RPEs, animals can infer predictions by learning the retrospective cause of rewards. Hence, whether mesolimbic dopamine instead conveys a causal associative signal that sometimes resembles RPE remains unknown. We developed an algorithm for retrospective causal learning and found that mesolimbic dopamine release conveys causal associations but not RPE, thereby challenging the dominant theory of reward learning. Our results reshape the conceptual and biological framework for associative learning.

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Learning causal relationships relies on understanding how often one event precedes another. To gain an understanding of how dopamine neuron activity and neurotransmitter release change when a retrospective relationship is degraded for a specific pair of events, we used outcome-selective Pavlovian contingency degradation in rats. Two cues were paired with distinct food rewards, one of which was also delivered in the absence of either cue. Conditioned approach was attenuated for the cue-reward contingency that was degraded. Dopamine neuron activity in the midbrain and dopamine release in the ventral striatum showed a profile of changes in cue- and reward-evoked responding that was not easily explained by a standard reinforcement learning model. An alternative model based on learning causal relationships was better able to capture evoked dopamine responses during contingency degradation, as well as conditioned behavior following optogenetic manipulations of dopamine during noncontingent rewards. Our results suggest that mesostriatal dopamine encodes the contingencies between meaningful events during learning.

Although the primary cause of acute coronary syndrome is atherosclerotic disease, it is important to include other causes of acute myocardial infarction. This report describes the case of a 53-year-old man with acute myeloid leukemia, who was referred to our cardiology department for treatment of acute myocardial infarction with ST segment elevation on an electrocardiogram. Portable echocardiography showed large areas of vegetation on the anterior mitral leaflet, while coronary angiography demonstrated the total occlusion of the left anterior descending artery. A histologic examination of the embolectomy specimen confirmed the presence of Aspergillus fungal thrombi. This report highlights a rare case of fatal Aspergillus endocarditis with myocardial infarction due to embolism in an immunosuppressed patient.