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The Journal of Neuroscience, May 21, 2008, 28(21):5611-5618; doi:10.1523/JNEUROSCI.5378-07.2008

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Development/Plasticity/Repair
Postsynaptic Action of Brain-Derived Neurotrophic Factor Attenuates 7 Nicotinic Acetylcholine Receptor-Mediated Responses in Hippocampal Interneurons

Catarina C. Fernandes, ^* António Pinto-Duarte, ^* Joaquim Alexandre Ribeiro, and Ana M. Sebastião

Institute of Pharmacology and Neurosciences, Faculty of Medicine and Unit of Neurosciences, Institute of Molecular Medicine, University of Lisbon, 1649-028 Lisbon, Portugal

Correspondence should be addressed to Catarina C. Fernandes, Avenida Prof. Egas Moniz, Edifício Egas Moniz, Piso B1, 1649-028 Lisbon, Portugal. Email: cfernandes{at}fm.ul.pt

Nicotinic mechanisms acting on the hippocampus influence attention, learning, and memory and constitute a significant therapeutic target for many neurodegenerative, neurological, and psychiatric disorders. Here, we report that brain-derived neurotrophic factor (BDNF) (1–100 ng/ml), a member of the neurotrophin gene family, rapidly decreases 7 nicotinic acetylcholine receptor responses in interneurons of the hippocampal CA1 stratum radiatum. Such effect is dependent on the activation of the TrkB receptor and involves the actin cytoskeleton; noteworthy, it is compromised when the extracellular levels of the endogenous neuromodulator adenosine are reduced with adenosine deaminase (1 U/ml) or when adenosine A_2A receptors are blocked with SCH 58261 (2-(2-furanyl)-7-(2-phenylethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine) (100 nM). The intracellular application of U73122 [GenBank] (1-[6[[(17β)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione) (5 µM), a broad-spectrum inhibitor of phospholipase C, or GF 109203X (bisindolylmaleimide I) (2 µM), a general inhibitor of protein kinase C isoforms, blocks BDNF-induced inhibition of 7 nicotinic acetylcholine receptor function. Moreover, in conditions of simultaneous intracellular dialysis of the fast Ca²⁺ chelator BAPTA (10 mM) and removal of extracellular Ca²⁺ ions, the inhibitory action of BDNF is further prevented. The present findings disclose a novel target for rapid actions of BDNF that might play important roles on synaptic transmission and plasticity in the brain.

Key words: brain-derived neurotrophic factor; TrkB receptor; nicotinic acetylcholine receptor; protein kinases; interneurons; hippocampus

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Received Dec. 5, 2007; revised March 17, 2008; accepted April 17, 2008.

Correspondence should be addressed to Catarina C. Fernandes, Avenida Prof. Egas Moniz, Edifício Egas Moniz, Piso B1, 1649-028 Lisbon, Portugal. Email: cfernandes{at}fm.ul.pt

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