Anatomical abnormalities in dopaminoceptive regions of the cerebral cortex of dopamine D1 receptor mutant mice

Alteration of dopamine neurotransmission during development can induce specific changes in neuronal structure and function. Here, we report specific morphological and neurochemical changes of projection neurons and interneurons of the medial frontal cortex of the dopamine D1 receptor null mouse. Using immunostaining of cytoskeletal proteins and a crossbred D1 receptor null:YFP transgenic reporter line, we demonstrate that the apical dendrites of pyramidal cells are abnormally organized in the prefrontal and anterior cingulate cortices of mice lacking the D1 receptor. Neuronal processes exhibit a decrease in bundling and an increase in irregular, tortuous patterning as they weave a course towards the pial surface. In addition, there is increased parvalbumin staining of the dendrites of cortical interneurons in D1 receptor null mice. Both pyramidal and interneuron alterations are evident by the early postnatal period and persist into adulthood. The alterations show regional specificity, in that dendritic profiles of projection neurons and interneurons in somatosensory and visual cortices develop normally. The abnormalities are reminiscent of those induced by prenatal exposure to cocaine in rabbits, an insult which has been shown to produce an attenuation of D1 receptor‐mediated responses through Gsα. These results suggest that loss of D1 receptor‐mediated signaling during development produces permanent alterations in the cellular organization of specific cortical areas involved in attention, cognition, and emotion. Pharmacological and behavioral studies in the D1 null mouse should be interpreted in the context of possible altered circuitry, given the presence of these developmental defects in the organization of dopaminoceptive regions of the cerebral cortex. J. Comp. Neurol. 487:270–282, 2005. © 2005 Wiley‐Liss, Inc.