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 K/MAP kinase pathway.

BDNF-TrkB signaling in striatopallidal neurons controls inhibition of locomotor behavior / D. Besusso, M. Geibel, D. Kramer, T. Schneider, V. Pendolino, B. Picconi, P. Calabresi, D.M. Bannerman, L. Minichiello. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 4:1(2013), pp. 2031.1-2031.12. [10.1038/ncomms3031]

BDNF-TrkB signaling in striatopallidal neurons controls inhibition of locomotor behavior

D. Besusso;
2013

Abstract

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 K/MAP kinase pathway.
Animals; 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; Mice; Mice, Knockout; Mice, Mutant Strains; Mitogen-Activated Protein Kinases; Neurons; Phosphorylation; Protein Kinase C; Receptor, trkB; Receptors, Dopamine D2; Synapses; Behavior, Animal; Locomotion; Signal Transduction
Settore BIO/14 - Farmacologia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/794553
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