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Uncontrolled drug-seeking and -taking behaviors are generally driven by maladaptive corticostriatal synaptic plasticity. The orbital frontal cortex (OFC) and its projections to the dorsomedial striatum (DMS) have been extensively implicated in drug-seeking and relapse behaviors. The influence of the synaptic plasticity of OFC projections to the DMS (OFC→DMS) on drug-seeking and -taking behaviors has not been fully characterized. To investigate this, we trained rats to self-administer 20% alcohol and then delivered an in vivo optogenetic protocol designed to induce long-term potentiation (LTP) selectively at OFC→DMS synapses. We selected LTP induction because we found that voluntary alcohol self-administration suppressed OFC→DMS transmission and LTP may normalize this transmission, consequently reducing alcohol-seeking behavior. Importantly, ex vivo slice electrophysiology studies confirmed that this in vivo optical stimulation protocol resulted in a significant increase in excitatory OFC→DMS transmission strength on day two after stimulation, suggesting that LTP was induced in vivo. Rat alcohol-seeking and -taking behaviors were significantly reduced on days 1-3, but not on days 7-11, after LTP induction. Striatal synaptic plasticity is modulated by several critical neurotransmitter receptors, including dopamine D1 receptors (D1Rs) and adenosine A2A receptors (A2ARs). We found that delivery of in vivo optical stimulation in the presence of a D1R antagonist abolished the LTP-associated decrease in alcohol-seeking behavior, whereas delivery in the presence of an A2AR antagonist may facilitate this LTP-induced behavioral change. These results demonstrate that alcohol-seeking behavior was negatively regulated by the potentiation of excitatory OFC→DMS neurotransmission. Our findings provide direct evidence that the OFC exerts "top-down" control of alcohol-seeking behavior via the DMS., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Animals engage in intricately woven and choreographed action sequences that are constructed from trial-and-error learning. The mechanisms by which the brain links together individual actions which are later recalled as fluid chains of behavior are not fully understood, but there is broad consensus that the basal ganglia play a crucial role in this process. This paper presents a comprehensive review of the role of the basal ganglia in action sequencing, with a focus on whether the computational framework of reinforcement learning can capture key behavioral features of sequencing and the neural mechanisms that underlie them. While a simple neurocomputational model of reinforcement learning can capture key features of action sequence learning, this model is not sufficient to capture goal-directed control of sequences or their hierarchical representation. The hierarchical structure of action sequences, in particular, poses a challenge for building better models of action sequencing, and it is in this regard that further investigations into basal ganglia information processing may be informative., (Copyright © 2019 Elsevier Ltd. All rights reserved.)