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The physiology of brain-derived neurotrophic factor signaling in enkephalinergic striatopallidal neurons is poorly understood. Changes in cortical Bdnf expression levels, and/or impairment in brain-derived neurotrophic factor anterograde transport induced by mutant huntingtin (mHdh) are believed to cause striatopallidal neuron vulnerability in early-stage Huntington's disease. Although several studies have confirmed a link between altered cortical brain-derived neurotrophic factor signaling and striatal vulnerability, it is not known whether the effects are mediated via the brain-derived neurotrophic factor receptor TrkB, and whether they are direct or indirect. Using a novel genetic mouse model, here, we show that selective removal of brain-derived neurotrophic factor-TrkB signaling from enkephalinergic striatal targets unexpectedly leads to spontaneous and drug-induced hyperlocomotion. This is associated with dopamine D2 receptor-dependent increased striatal protein kinase C and MAP kinase activation, resulting in altered intrinsic activation of striatal enkephalinergic neurons. Therefore, brain-derived neurotrophic factor/TrkB signaling in striatopallidal neurons controls inhibition of locomotor behavior by modulating neuronal activity in response to excitatory input through the protein kinase C/MAP kinase pathway.

Original publication




Journal article


Nat Commun

Publication Date





Animals, Behavior, Animal, Brain-Derived Neurotrophic Factor, Cocaine, Dopamine and cAMP-Regulated Phosphoprotein 32, Enkephalins, Enzyme Activation, Excitatory Postsynaptic Potentials, Gait, Gene Deletion, Globus Pallidus, Green Fluorescent Proteins, Integrases, Locomotion, Mice, Mice, Knockout, Mice, Mutant Strains, Mitogen-Activated Protein Kinases, Neurons, Phosphorylation, Protein Kinase C, Receptor, trkB, Receptors, Dopamine D2, Signal Transduction, Synapses