mesocortical

Mesocortical refers to a dopaminergic pathway originating primarily from the ventral tegmental area (VTA) that projects to the prefrontal cortex and related cortical regions. It is part of the broader mesocorticolimbic dopamine system, distinct from the mesolimbic pathway that targets limbic structures such as the nucleus accumbens.

Anatomy and function: Neurons originate in the VTA and project to the prefrontal cortex, including the dorsolateral, ventromedial, and medial prefrontal cortex, as well as the orbitofrontal cortex and anterior cingulate. Through these projections, dopamine modulates executive functions, working memory, attention, decision making, and motivational aspects of behavior. Dopamine signaling in this pathway interacts with glutamatergic inputs and follows an inverted-U relationship with cognitive performance, where both too little and too much dopamine can impair function.

Neurochemistry: In the prefrontal cortex, dopamine acts predominantly on D1-like receptors to regulate neuronal excitability and cortical network dynamics. The mesocortical system is driven by a balance of tonic and phasic VTA firing, and its activity can be influenced by factors such as stress, drugs, and other neuromodulators.

Clinical significance: Alterations in mesocortical dopamine transmission have been implicated in schizophrenia, particularly in negative symptoms and cognitive deficits. Some pharmacological strategies aim to enhance mesocortical function or address its dysregulation, including certain atypical antipsychotics and compounds that modulate D1 receptor activity or glutamatergic signaling. The term is also discussed in relation to mood and attention disorders.