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BDNF and Synaptic Plasticity, Cognitive Function, and Dysfunction

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Neurotrophic Factors

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 220))

Abstract

Among all neurotrophins, brain-derived neurotrophic factor (BDNF) stands out for its high level of expression in the brain and its potent effects on synapses. It is now widely accepted that the main function of BDNF in the adult brain is to regulate synapses, with structural and functional effects ranging from short-term to long-lasting, on excitatory or inhibitory synapses, in many brain regions. The diverse effects of BDNF on brain synapses stem from its complex downstream signaling cascades, as well as the diametrically opposing effects of the pro- and mature form through distinct receptors, TrkB and p75NTR. Many aspects of BDNF cell biology are regulated by neuronal activity. The synergistic interactions between neuronal activity and synaptic plasticity by BDNF make it an ideal and essential regulator of cellular processes that underlie cognition and other complex behaviors. Indeed, numerous studies firmly established that BDNF plays a critical role in hippocampal long-term potentiation (LTP), a long-term enhancement of synaptic efficacy thought to underlie learning and memory. Converging evidence now strongly suggest that deficits in BDNF signaling contribute to the pathogenesis of several major diseases and disorders such as Huntington’s disease, Alzheimer’s disease, and depression. Thus, manipulating BDNF pathways represents a viable treatment approach to a variety of neurological and psychiatric disorders.

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Abbreviations

BDNF:

Brain-derived neurotrophic factor

BDNF-KIV:

BDNF GFP knockin in exon IV

CA1/CA3:

Cornu ammonis areas 1 and 3

E-LTP:

Early phase long-term potentiation

GAD:

Glutamate decarboxylase

HA:

Hemagglutinin

HFS:

High frequency stimulation

IgG:

Immunoglobulin

KO:

Knockout

L-LTP:

Late phase long-term potentiation

LTD:

Long-term depression

mBDNF:

Mature BDNF

MMP:

Matrix metalloprotease

MRI:

Magnetic resonance imaging

NMDAR:

N-methyl-d-aspartate receptor

p75NTR :

p75 neurotrophin receptor

proBDNF:

Precursor BDNF

PRP:

Plasticity-related protein

PV:

Parvalbumin

SNP:

Single nucleotide polymorphism

STDP:

Spike time-dependent plasticity

TBS:

Theta burst stimulation

tDCS:

Transcranial direct current stimulation

tPA:

Tissue plasminogen activator

TrkB:

Tropomyosin-related kinase B

UTR:

Untranslated region

Val66Met:

Valine 66 to methionine

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Authors and Affiliations

  1. GlaxoSmithKline, R&D China, Building 3, 898 Halei Road, Zhangjiang Hi-tech Park, Pudong, Shanghai, 201203, China

    B. Lu & G. Nagappan

  2. Department of Psychiatry, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USA

    Y. Lu

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  1. B. Lu
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  3. Y. Lu
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Correspondence to B. Lu .

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  1. Department of Neuroscience, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany

    Gary R. Lewin

  2. Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee, USA

    Bruce D. Carter

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Lu, B., Nagappan, G., Lu, Y. (2014). BDNF and Synaptic Plasticity, Cognitive Function, and Dysfunction. In: Lewin, G., Carter, B. (eds) Neurotrophic Factors. Handbook of Experimental Pharmacology, vol 220. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-45106-5_9

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