Learning deficits are a major clinical problem affecting children with neurofibromatosis type 1 (NF1). Using novel genetically-engineered mouse strains, Dr. Ype Elgersma, from the Erasmus Medical Center in the Netherlands, determined how brain cells control learning and memory retrieval.
Dr. Elgersma, working with colleagues in the Washington University NF Center, demonstrated that Nf1 mouse strains have increased levels of brain cell inhibition, which causes the learning deficits in these mice. In their new study, they uncovered the mechanism responsible for this inhibition. Specifically, they found that hyperpolarization-activated cyclic nucleotide-gated (HCN) currents are the cause for the increased brain cell inhibition in Nf1 mice. Importantly, they were able to correct the learning deficits in Nf1 mice by targeting the HCN channel with the drug lamotrigine.
Omrani A, van der Vaart T, Mientjes E, van Woerden GM, Hojjati MR, Li KW, Gutmann DH, Levelt CN, Smit AB, Silva AJ, Kushner SA, Elgersma Y. HCN channels are a novel therapeutic target for cognitive dysfunction in Neurofibromatosis type 1. Mol Psychiatry. 2015 Apr 28, doi:10.1038/mp.2015.48.