Postsynaptic BDNF-TrkB Signaling in Synapse Maturation, Plasticity, and Disease

Overview

Journal Dev Neurobiol

Specialties Biology
Neurology

Date 2010 Feb 27

PMID 20186705

Citations 313

Authors

Akira Yoshii

Martha Constantine-Paton

Affiliations

Soon will be listed here.

Abstract

Brain-derived neurotrophic factor (BDNF) is a prototypic neurotrophin that regulates diverse developmental events from the selection of neural progenitors to the terminal dendritic differentiation and connectivity of neurons. We focus here on activity-dependent synaptic regulation by BDNF and its receptor, full length TrkB. BDNF-TrkB signaling is involved in transcription, translation, and trafficking of proteins during various phases of synaptic development and has been implicated in several forms of synaptic plasticity. These functions are carried out by a combination of the three signaling cascades triggered when BDNF binds TrkB: The mitogen-activated protein kinase (MAPK), the phospholipase Cgamma (PLC PLCgamma), and the phosphatidylinositol 3-kinase (PI3K) pathways. MAPK and PI3K play crucial roles in both translation and/or trafficking of proteins induced by synaptic activity, whereas PLCgamma regulates intracellular Ca(2+) that can drive transcription via cyclic AMP and a protein kinase C. Conversely, the abnormal regulation of BDNF is implicated in various developmental and neurodegenerative diseases that perturb neural development and function. We will discuss the current state of understanding BDNF signaling in the context of synaptic development and plasticity with a focus on the postsynaptic cell and close with the evidence that basic mechanisms of BDNF function still need to be understood to effectively treat genetic disruptions of these pathways that cause devastating neurodevelopmental diseases.

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References

Tanaka T, Saito H, Matsuki N . Inhibition of GABAA synaptic responses by brain-derived neurotrophic factor (BDNF) in rat hippocampus. J Neurosci. 1997; 17(9):2959-66. PMC: 6573653. View

Shaywitz A, Greenberg M . CREB: a stimulus-induced transcription factor activated by a diverse array of extracellular signals. Annu Rev Biochem. 2000; 68:821-61. DOI: 10.1146/annurev.biochem.68.1.821. View

Ehrlich I, Klein M, Rumpel S, Malinow R . PSD-95 is required for activity-driven synapse stabilization. Proc Natl Acad Sci U S A. 2007; 104(10):4176-81. PMC: 1820728. DOI: 10.1073/pnas.0609307104. View

Matsumoto T, Rauskolb S, Polack M, Klose J, Kolbeck R, Korte M . Biosynthesis and processing of endogenous BDNF: CNS neurons store and secrete BDNF, not pro-BDNF. Nat Neurosci. 2008; 11(2):131-3. DOI: 10.1038/nn2038. View

Amaral M, Pozzo-Miller L . TRPC3 channels are necessary for brain-derived neurotrophic factor to activate a nonselective cationic current and to induce dendritic spine formation. J Neurosci. 2007; 27(19):5179-89. PMC: 2806846. DOI: 10.1523/JNEUROSCI.5499-06.2007. View

Gruart A, Sciarretta C, Valenzuela-Harrington M, Delgado-Garcia J, Minichiello L . Mutation at the TrkB PLC{gamma}-docking site affects hippocampal LTP and associative learning in conscious mice. Learn Mem. 2007; 14(1):54-62. PMC: 1838546. DOI: 10.1101/lm.428307. View

Meikle L, Pollizzi K, Egnor A, Kramvis I, Lane H, Sahin M . Response of a neuronal model of tuberous sclerosis to mammalian target of rapamycin (mTOR) inhibitors: effects on mTORC1 and Akt signaling lead to improved survival and function. J Neurosci. 2008; 28(21):5422-32. PMC: 2633923. DOI: 10.1523/JNEUROSCI.0955-08.2008. View

Yoshii A, Constantine-Paton M . BDNF induces transport of PSD-95 to dendrites through PI3K-AKT signaling after NMDA receptor activation. Nat Neurosci. 2007; 10(6):702-11. DOI: 10.1038/nn1903. View

Huang Z, Kirkwood A, Pizzorusso T, Porciatti V, Morales B, Bear M . BDNF regulates the maturation of inhibition and the critical period of plasticity in mouse visual cortex. Cell. 1999; 98(6):739-55. DOI: 10.1016/s0092-8674(00)81509-3. View

10.

Wardle R, Poo M . Brain-derived neurotrophic factor modulation of GABAergic synapses by postsynaptic regulation of chloride transport. J Neurosci. 2003; 23(25):8722-32. PMC: 6740427. View

11.

Malenka R, Bear M . LTP and LTD: an embarrassment of riches. Neuron. 2004; 44(1):5-21. DOI: 10.1016/j.neuron.2004.09.012. View

12.

Sanchez A, Matthews B, Meynard M, Hu B, Javed S, Cohen Cory S . BDNF increases synapse density in dendrites of developing tectal neurons in vivo. Development. 2006; 133(13):2477-86. DOI: 10.1242/dev.02409. View

13.

Leibrock J, Lottspeich F, Hohn A, Hofer M, Hengerer B, Masiakowski P . Molecular cloning and expression of brain-derived neurotrophic factor. Nature. 1989; 341(6238):149-52. DOI: 10.1038/341149a0. View

14.

Ehrlich I, Malinow R . Postsynaptic density 95 controls AMPA receptor incorporation during long-term potentiation and experience-driven synaptic plasticity. J Neurosci. 2004; 24(4):916-27. PMC: 6729816. DOI: 10.1523/JNEUROSCI.4733-03.2004. View

15.

Rosch H, Schweigreiter R, Bonhoeffer T, Barde Y, Korte M . The neurotrophin receptor p75NTR modulates long-term depression and regulates the expression of AMPA receptor subunits in the hippocampus. Proc Natl Acad Sci U S A. 2005; 102(20):7362-7. PMC: 1129133. DOI: 10.1073/pnas.0502460102. View

16.

Soppet D, Escandon E, Maragos J, Middlemas D, Reid S, Blair J . The neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 are ligands for the trkB tyrosine kinase receptor. Cell. 1991; 65(5):895-903. DOI: 10.1016/0092-8674(91)90396-g. View

17.

Chahrour M, Jung S, Shaw C, Zhou X, Wong S, Qin J . MeCP2, a key contributor to neurological disease, activates and represses transcription. Science. 2008; 320(5880):1224-9. PMC: 2443785. DOI: 10.1126/science.1153252. View

18.

Tyler W . BDNF enhances quantal neurotransmitter release and increases the number of docked vesicles at the active zones of hippocampal excitatory synapses. J Neurosci. 2001; 21(12):4249-58. PMC: 2806848. View

19.

Shimada A, Mason C, Morrison M . TrkB signaling modulates spine density and morphology independent of dendrite structure in cultured neonatal Purkinje cells. J Neurosci. 1998; 18(21):8559-70. PMC: 6793520. View

20.

Sklar P, Gabriel S, McInnis M, Bennett P, Tsan G, Schaffner S . Family-based association study of 76 candidate genes in bipolar disorder: BDNF is a potential risk locus. Brain-derived neutrophic factor. Mol Psychiatry. 2002; 7(6):579-93. DOI: 10.1038/sj.mp.4001058. View