Abstract

The BDNF Val66Met polymorphism alters cortico-striatal neurotransmission in mice.

I. Ninan; K.G. Bath; K. Dagar; R. Perez-Castro; F.S. Lee; M.V. Chao
Society for Neuroscience. 2010.

Abstract

It is widely believed that the striatal neurons depend on cortical afferents for their BDNF trophic support. Activity-dependent release of BDNF from the cortical neurons may be critical for the striatal neurotransmission and plasticity. The Val66Met human polymorphism in the brain-derived neurotrophic factor (BDNF) gene results in a defect in regulated release of BDNF and affects "cognitive" functions and "affective" behaviors. In this study, we investigated cortico-striatal neurotransmission in BDNFMet/Met mice, a variant BDNF Val66Met mouse with a defect in the regulated release of BDNF. While a reduction in population spike amplitude was found in the dorsomedial striatum, the dorsolateral striatum showed an enhanced population spike amplitude in BDNFMet/Met mice. Consistent with the reduced neurotransmission in the dorsomedial striatum, we found a reduction in early rotarod performance in BDNFMet/Met mice. On the other hand, BDNFMet/Met mice performed better than wild-type animals in the later stages of rotarod training that depend on the dorsolateral striatum. Both the electrophysiological and behavioral studies suggest that the BDNF Val66Met polymorphism affects activity-dependent release of BDNF in the striatum, resulting in a regional imbalance of cortico-striatal neurotransmission. The Val66Met polymorphism-induced alterations in cortico-striatal neurotransmission might play a role in neurodegenerative diseases like Huntington's disease.