Candidate Review:

Examining the Effects of Dopamine System Stimulation During Cortical Axon Guidance

Stephanie Bronson* and Christine L. Konradi§

*Neuroscience Graduate Program, Vanderbilt University Medical School, U1205 Medical Center North, Nashville, TN 37232, USA.
§Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA.
Correspondence to S.B. e-mail: stephanie.e.bronson@vanderbilt.edu

Abstract | Full Text | PDF

ABSTRACT | Dopamine (DA) is a modulatory neurotransmitter that mediates motor function and emotion-based behaviors. Dopaminergic projections throughout the cerebral cortex innervate brain regions implicated in the pathophysiology of neuropsychiatric illnesses such as Parkinson’s disease (PD), schizophrenia, and mood disorders. DA is vital to normal brain function and is also involved in sleep, aggression, reward, and appetite. However, the role DA plays during development of the central nervous system has not been fully elucidated.The arrival of DA fibers in the cortex is concurrent with the development of cortical projections and axonal pathfinding of cortical efferents1. Recently DA has been shown to affect the migration of interneurons to the cerebral cortex. Animals treated with drugs that increase dopaminergic tone upregulate expression of the axon guidance factor receptors DCC and Unc5c and show neuroanatomical changes in the prefrontal cortex (PFC), a brain region adversely affected in schizophrenia. In addition, DA receptor activation triggers downstream effectors that influence cellular levels of cyclic nucleotides and PKA activity, both of which play a role in growth cone steering and cytoskeletal reformation. Understanding the role of DA receptor activation during development is relevant to the field of psychiatry as schizophrenia is typically first seen in late adolescence and pharmacological treatments for the disorder target D2 DA receptors. This review will examine data that address the role of DA in cortical development, specifically axon guidance. Understanding how DA affects the formation of cortical circuits may shed light on how the DA system functions in diseased brains.