Dopamine is an important transmitter involved in responses to novelty, attention, motor control and cognitive functions. Although the brain projections that use this transmitters are many, the projection from the ventral tegmental area to the nucleus accumbens (known as mesolimbic system) stands out as very important for the brain functions mentioned above, and it is known to be involved in drug addiction and schizophrenia. Despite this obvious importance, the precise nature of how dopamine exerts control of information processing in the nucleus accumbens is not completely understood. The past couple of decades have provided important information in this regard; yet, an integrative perspective is missing. Here we plan to assess how dopamine modulates the response of accumbens neurons to their primary excitatory inputs. We will test this by delivering drugs that activate dopamine receptors and by stimulating the brain systems that provide this innervation, yielding release of endogenous dopamine. We will test the effects of both exogenous and endogenous dopamine both in intact (anesthetized) animals and in brain slices. The latter preparation will allow us exquisite manipulations to unveil the cellular mechanisms involved in the actions of dopamine. In addition, some experiments will be conducted in awake animals by way of implanting microwires that allow recording electrical activity of populations of neurons as well as from individual neurons. The prediction that during times in which dopamine neurons are known to fire intensely (i.e., in presence of reward or a reward-predicting stimulus) there will be a synchronous activation of ensembles of neurons in the accumbens will be tested with simultaneous recordings. Another component in these circuits that has emerged recently as having important contributions to shaping the information flow in the accumbens is the less-studied subset of interneurons. These are inhibitory neurons that may exert a strong control over the primary neurons and can be activated by dopamine. We will test this issue by conducting parallel in vivo and in vitro studies on the effects of dopamine and selective activation of its receptors on the activity of identified interneurons. These experiments will provide a clearer picture of how dopamine may affect the manner accumbens neurons can be activated and the role of this important transmitter on network properties of these circuits, which are critically involved in drug abuse and psychiatric conditions.
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