QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, August 27, 2008, 28(35):8677-8681; doi:10.1523/JNEUROSCI.2440-08.2008

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Wang, H. Articles by Lee, H.-K. Search for Related Content PubMed PubMed Citation Articles by Wang, H. Articles by Lee, H.-K. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB CALCIUM COMPOUNDS CALCIUM, ELEMENTAL

 Previous Article  |  Next Article 

Brief Communications
BACE1 Knock-Outs Display Deficits in Activity-Dependent Potentiation of Synaptic Transmission at Mossy Fiber to CA3 Synapses in the Hippocampus

Hui Wang,^1,2 Lihua Song,¹ Fiona Laird,^3,4 Philip C. Wong,^3,4 and Hey-Kyoung Lee^1,2

¹Department of Biology, College of Chemical and Life Sciences, and ²Neuroscience and Cognitive Science Program, University of Maryland, College Park, Maryland 20742, and Departments of ³Pathology and ⁴Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Correspondence should be addressed to Hey-Kyoung Lee, Department of Biology, University of Maryland, 1210 Biology–Psychology Building, College Park, MD 20742. Email: hlee21{at}umd.edu

β-Amyloid precursor protein cleavage enzyme 1 (BACE1) has been identified as a major neuronal β-secretase critical for the formation of β-amyloid (Aβ) peptide, which is thought responsible for the pathology of Alzheimer's disease (AD). Therefore, BACE1 is one of the key therapeutic targets that can prevent the progression of AD. Previous studies showed that knocking out the BACE1 gene prevents Aβ formation, but results in behavioral deficits and specific synaptic dysfunctions at Schaffer collateral to CA1 synapses. However, BACE1 protein is most highly expressed at the mossy fiber projections in CA3. Here, we report that BACE1 knock-out mice display reduced presynaptic function, as measured by an increase in paired-pulse facilitation ratio. More dramatically, mossy fiber long-term potentiation (LTP), which is normally expressed via an increase in presynaptic release, was eliminated in the knock-outs. Although long-term depression was slightly larger in the BACE1 knock-outs, it could not be reversed. The specific deficit in mossy fiber LTP was upstream of cAMP signaling and could be "rescued" by transiently elevating extracellular Ca²⁺ concentration. These results suggest that BACE1 may play a critical role in regulating presynaptic function, especially activity-dependent strengthening of presynaptic release, at mossy fiber synapses.

Key words: long-term potentiation; long-term depression; presynaptic; paired-pulse facilitation; beta-secretase; Alzheimer's disease

---

Received May 30, 2008; revised July 11, 2008; accepted July 19, 2008.

Correspondence should be addressed to Hey-Kyoung Lee, Department of Biology, University of Maryland, 1210 Biology–Psychology Building, College Park, MD 20742. Email: hlee21{at}umd.edu

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help