Abstract
Dysregulation of the dopamine system is central to many models of the pathophysiology of psychosis in schizophrenia. However, emerging evidence suggests that this dysregulation is driven by the disruption of upstream circuits that provide afferent control of midbrain dopamine neurons. Furthermore, stress can profoundly disrupt this regulatory circuit, particularly when it is presented at critical vulnerable prepubertal time points. This review will discuss the dopamine system and the circuits that regulate it, focusing on the hippocampus, medial prefrontal cortex, thalamic nuclei, and medial septum, and the impact of stress. A greater understanding of the regulation of the dopamine system and its disruption in schizophrenia may provide a more complete neurobiological framework to interpret clinical findings and develop novel treatments.
Highlights
Dopamine (DA) modulates circuit reactivity based on environmental stimuli and prior experience and plays a central role in functions including reward processing, reinforcement, and habit formation [1,2,3]
We discuss evidence indicating the involvement of the medial prefrontal cortex, thalamic nuclei, and medial septum on the ventral tegmental area (VTA) DA system and how changes in the activity of these regions may lead to a hyperdopaminergic state as seen in schizophrenia
We showed that activation of the nucleus reuniens increases DA neuron population activity in the VTA via its projection to the ventral subiculum of the hippocampus (vHipp), since it was prevented by vHipp inactivation [93]
Summary
Dopamine (DA) modulates circuit reactivity based on environmental stimuli and prior experience and plays a central role in functions including reward processing, reinforcement, and habit formation [1,2,3]. Dysregulation of the DA system has been fundamental to many models of the pathophysiology of schizophrenia [7, 8]. It is implicated in psychotic symptoms, which involve profound perceptual disturbances (hallucinations) and fixed beliefs resistant to contradictory evidence (delusions). Psychotic symptoms can be attenuated by D2 receptor blocking drugs [10, 11] that reduce the abnormal increased DA neuron activity [12,13,14], but the underlying cognitive processes likely involve complex connections between numerous brain regions that remain dysfunctional. This article will discuss some of the circuits that regulate DA neuron activity and how dysfunction in these upstream circuits may influence the DA system in schizophrenia
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
