Dr. Susana Mingote’s research has identified key mechanisms through which the dopamine system regulates motivated behavior. In a rat, dopamine depletions in nucleus accumbens reduce the motivation to work for large rewards, making the animal prefer effortless behaviors associated with much smaller food rewards. Interestingly, increasing adenosine signaling in the nucleus accumbens produced similar reductions in motivation. Adenosine is release by astrocytes, so her work has showed for the first time that the activity of dopamine neurons and astrocytes in the nucleus accumbens has the opposite effects on motivation. Furthermore, blocking adenosine signaling using adenosine A2A receptors antagonists improves motivation and may alleviate symptoms of fatigue and anergia in depression. In another line of research, Dr. Mingote focuses on the function of subtype of dopamine neurons capable of co-releasing glutamate. Her research in mice discovered that this small population of neurons regulates motivated behavior by signaling the salience of cues in the environment. Aberrant salience processing is thought to underlie the development of psychosis in schizophrenia, and this work suggests that the activity of dopamine/glutamate neurons and their interaction with astrocytes play a key role the psychopathology of schizophrenia.
One of the biggest challenges of navigating through sensory-complex environments, such as New York City, is to limit our attention to important events. Our choices are often driven by salience, meaning the features of an event that stands out in a particular context. Through behavioral experience, we learn ignore irrelevant contextual cues, while avoiding cues associated with harmful environments and pursue those that lead to gratifying ones. The precise association of environmental cues with a particular behavioral experience determines our ability to adapt to complex environments and is an essential survival skill that is often impaired in a number of neuropsychiatric disorders. Dr. Mingote’s research in mice aims to understand how the brain forms and updates the memory of salient events to discriminate between harmful, rewarding, or neutral environments in both healthy and diseased conditions. Her group is particularly interested in how dopamine neuron projections to the lateral entorhinal cortex modulate memory of salience events, and how neuron-astrocyte interactions are involved in this memory process. The goal is to identify neuron and glial adaptations underlying aberrant salience processing in psychiatric disorders such as schizophrenia.