The ventral pallidum (VP) is a central node in the reward system that is strongly implicated in reward and addiction. Although the majority of VP neurons are GABAergic and encode reward, recent studies revealed a novel glutamatergic neuronal population in the VP [VP neurons expressing the vesicular glutamate transporter 2 (VP VGluT2)], whose activation generates aversion. Withdrawal from drugs has been shown to induce drastic synaptic changes in neuronal populations associated with reward, such as the ventral tegmental area (VTA) or nucleus accumbens neurons, but less is known about cocaine-induced synaptic changes in neurons classically linked with aversion. Here, we demonstrate that VP VGluT2 neurons contact different targets with different intensities, and that cocaine conditioned place preference (CPP) training followed by abstinence selectively potentiates their synapses on targets that encode aversion. Using whole-cell patch-clamp recordings combined with optogenetics in male and female transgenic mice, we show that VP VGluT2 neurons preferentially contact aversion-related neurons, such as lateral habenula neurons and VTA GABAergic neurons, with minor input to reward-related neurons, such as VTA dopamine and VP GABA neurons. Moreover, after cocaine CPP and abstinence, the VP VGluT2 input to the aversionrelated structures is potentiated, whereas the input to the reward-related structures is depressed. Thus, cocaine CPP followed by abstinence may allow VP VGluT2 neurons to recruit aversion-related targets more readily and therefore be part of the mechanism underlying the aversive symptoms seen after withdrawal.

Neurons in the motor areas of cortex play a key role in associating sensory instructions with movements. However, their ability to acquire and maintain representations of novel stimulus features, especially when these features are behaviorally relevant, remains unknown. We investigated neuronal changes in these areas during and after associative learning, by training monkeys on a novel reaching task that required associating target colors with movement directions. Before and after learning, the monkeys performed a well known center-out task. We found that during learning, up to 48% of the neurons developed learning-related responses, differentiating between the associative task and the center-out task, although movement kinematics were the same. After learning, on returning to the center-out task in which color was irrelevant, many of these neurons maintained their response to the associative task; they displayed novel sensitivity to the color of the target that was relevant during learning. These neuronal responses prevailed in both the primary motor cortex and the ventral and dorsal premotor cortices, without degrading the information that the neurons firing carried about movement direction. Our results show that motor cortical neurons can rapidly develop and maintain sensitivities to novel arbitrary sensory features such as color, when such features are behaviorally relevant.

Obesity results from overconsumption of energy, partly because of the inability to refrain from highly palatable rewarding foods. Even though palatable food is available to everyone, only a fraction of the population develops obesity. We previously showed that following chronic exposure to highly palatable food animals that gained the most weight also showed addictive-like motivation to seek for palatable food. An important question remains-is this extreme, addictive-like, motivation to consume palatable food the cause or the consequence of diet-induced obesity? Here, we show that obesity-prone (OP) mice exhibit higher motivation for palatable food consumption compared with obesity-resistant mice even before developing obesity, but that the full manifestation of this high motivation to eat is expressed only after chronic exposure to high-fat-high-sugar (HFHS) diet. HFHS diet also impairs performance in the operant food-seeking task selectively in OP mice, an impairment that persists even after 2 weeks of abstinence from HFHS food. Overall, our data suggest that while some aspects of food motivation are high in OP mice already before developing obesity, the chronic exposure to HFHS food accentuates it and drives the development of obesity.

Some motor tasks, if learned together, interfere with each other's consolidation and subsequent retention, whereas other tasks do not. Interfering tasks are said to employ the same internal model whereas noninterfering tasks use different models. The division of function among internal models, as well as their possible neural substrates, are not well understood. To investigate these questions, we compared responses of single cells in the primary motor cortex and premotor cortex of primates to interfering and noninterfering tasks. The interfering tasks were visuomotor rotation followed by opposing visuomotor rotation. The noninterfering tasks were visuomotor rotation followed by an arbitrary association task. Learning two noninterfering tasks led to the simultaneous formation of neural activity typical of both tasks, at the level of single neurons. In contrast, and in accordance with behavioral results, after learning two interfering tasks, only the second task was successfully reflected in motor cortical single cell activity. These results support the hypothesis that the representational capacity of motor cortical cells is the basis of behavioral interference and division between internal models.

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