Dopamine D2 receptors are important for various brain functions such as learning and working memory. Abnormal D2 receptor signaling has been implicated in schizophrenia. In this paper, Jia and colleagues report that activation of D2 receptors in mice reduces spine number by NMDA glutamate receptor- (GluN2B) and cyclic AMP-dependent mechanisms, and that this regulation occurred only during adolescence. During this time period, D2 receptor overactivation caused by mutations in the schizophrenia risk gene Dtnbp1 led to spine deficiency, dysconnectivity in the entorhinal-hippocampal circuit and impairment of spatial working memory. These defects could be improved by D2 receptor blockers administered during adolescence. The authors concluded that D2 dopamine receptors are involved in spine development, and that D2 receptor dysfunction during adolescence impairs neuronal circuits and working memory. They suggest that treatments during adolescence to prevent aberrant D2 receptor activity may protect against cognitive impairment.
Jia JM, Zhao J, Hu Z, Lindberg D, Li Z: Age-dependent regulation of synaptic connections by dopamine D2 receptors. Nature Neuroscience 16(11): 1627-1636 (2013).