Candidate Review:

Modulation of Neuronal Differentiation by Dopamine Receptors

Fazal Arain

Neuroscience Graduate Program, Vanderbilt University School of Medicine, U1205 Medical Center North, Nashville, TN 37232, USA.
Correspondence e-mail: fazal.m.arain.1@vanderbilt.edu

Abstract | Full Text | PDF

Abstract | Brain development is a prolonged process that requires a tight regulation of spatiotemporal events. Neuropsychiatric disorders, like schizophrenia and bipolar disorder have been hypothesized to have a developmental etiology despite the fact that the manifestations of the symptoms of these diseases occur later in life. It has been suggested that developmental perturbation of neuronal architecture in specific regions of the forebrain is responsible for the manifestations of these diseases. Dopamine is a neurotransmitter that appears prior to synaptogenesis and expression of the dopamine system is particularly high in the regions implicated in neuropsychiatric disorders. The receptors for dopamine are classified into two sub-families which trigger unique intracellular signaling cascades and modulation of the physiology of these receptors appear to result in permanent alteration in the morphology of dopaminoceptive neurons. A number of approaches, that include modulation of activity of these receptors by different chemical compounds, altered receptor trafficking and developmental deletion of dopamine receptors, have complemented these conclusions. It appears that modulation of neuronal morphology depends upon the type of dopamine receptor activated, the distinct intracellular signaling cascade triggered and the region of the brain that express these neurons. The cellular mechanisms involved in the modulation of neuronal morphology are still under investigation. Alterations in the intracellular calcium ion concentration upon activation of dopamine receptors could lead to the triggering of down stream signals linked to the modulation of neuronal cytoskeleton and hence neuronal morphology. Studies conducted on receptor-specific modulation of neuronal differentiation could help us better understand the pathophysiology of neuropsychiatric disorders.