Dopamine deficiency underlies learning deficits in neurofibromatosis-1 mice


Address correspondence to Dr Gutmann, Department of Neurology, Box 8111, 660 South Euclid Avenue, St Louis, MO 63110. E-mail:


Children with neurofibromatosis type 1 (NF1) are prone to learning and behavioral abnormalities, including problems with spatial learning and attention. The molecular etiology for these deficits is unclear, as previous studies have implicated defective dopamine, cyclic adenosine monophosphate (cAMP), and Ras homeostasis. Using behavioral, electrophysiological, and primary culture, we now demonstrate that reduced dopamine signaling is responsible for cAMP-dependent defects in neuron function and learning. Collectively, these results establish defective dopaminergic function as a contributing factor underlying impaired spatial learning and memory in children and adults with NF1, and support the use of treatments that restore normal dopamine homeostasis for select individuals. ANN NEUROL 2013;73:309–315