Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Sci. Signal., 25 August 2009
Vol. 2, Issue 85, p. ec284
[DOI: 10.1126/scisignal.285ec284]

EDITORS' CHOICE

Neuroscience Minimizing Plasticity

Elizabeth M. Adler

Science Signaling, AAAS, Washington, DC 20005, USA

Although the mechanisms underlying long-term potentiation (LTP) of glutamatergic synapses have been intensively investigated, less is known about processes that may minimize this form of synaptic plasticity in particular brain regions. For instance, although synapses on pyramidal cells in the CA1 region of the hippocampus show robust LTP, neurons in the CA2 region rarely show LTP. LTP at CA1 synapses depends on activity-dependent increases in postsynaptic Ca2+ concentration, leading Simons at al. to investigate Ca2+-handling mechanisms in CA2 neurons. Fluorescence imaging revealed that action potential–initiated transient changes in the free Ca2+ concentration of dendritic spines of CA2 neurons were smaller than those of CA1 neurons. Analyses of the effects of exogenous Ca2+ buffer indicated that dendrites in CA2 neurons experienced similar changes in total Ca2+ and that the attenuated increase in free Ca2+ had to do with increased endogenous buffering capacity and Ca2+ extrusion mechanisms. Indeed, increasing extracellular Ca2+ concentration (and thereby the Ca2+ transient) enabled the induction of LTP in CA2 neurons; under these conditions, CA2 LTP, like CA1 LTP, was inhibited by antagonizing the NMDA-type glutamate receptor (a key route of Ca2+ influx). Although the CA2 neurons had increased buffering capacity, this element alone seemed insufficient to entirely account for their lack of LTP. Noting that Pep-19 (a protein that interacts with the Ca2+-binding protein calmodulin and thereby influences Ca2+ dynamics) is abundant in CA2 neurons but not CA1 neurons, the authors introduced camstatin, a functional fragment of Pep-19, into CA1 neurons. They found that camstatin blocked LTP and enhanced Ca2+ extrusion mechanisms, with little effect on Ca2+ buffering, Ca2+ influx, or the unpotentiated synaptic response. In contrast, inhibiting the plasma membrane Ca2+ ATPase (which interacts with calmodulin) in CA2 neurons enabled the induction of LTP. Thus, the authors conclude that CA2 neurons do indeed have the capacity for LTP, but their ability to do so is held in check by Ca2+ buffering, extrusion, or both.

S. B. Simons, Y. Escobedo, R. Yasuda, S. M. Dudek, Regional differences in hippocampal calcium handling provide a cellular mechanism for limiting plasticity. Proc. Natl. Acad. Sci. U.S.A. 106, 14080–14084 (2009). [Abstract] [Full Text]

Citation: E. M. Adler, Minimizing Plasticity. Sci. Signal. 2, ec284 (2009).



To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882