Two-photon uncaging strikes again!

In this week's issue of Science (28 March 2008) Kasai's lab has another paper using 2P uncaging of glutamate at single spine heads. In this latest effort they add a fresh technical twist to their arsenal. Previously Kasai's lab had mimicked electrical LTP at single spine heads by pairing uncaging with postsynaptic depolarisation (Nature 2004). Now they mimic spike-timing dependent plasticity by uncaging a quantal amount of glutamate a few milliseconds before a postsynaptic spike. Doing this 80 times induces a different sort of LTP at the stimulated spine. They call these protocols "conventional LTP" and "spike-timing LTP". The latter turns out to (A) largely depedent upon protein synthesis and BDNF autocrine secretion, and (B) much more temporally gradual than the conventional LTP.
Svoboda's lab have tried a different spike timing protocol in their recent Nature paper. But the n=4 of their Figure 4d makes comparison difficult, but they do report spine head enlargement accompanied by AMPA-R current increases.
Kasai's idea is that localised Ca entry drives an initial LTP that may provide a tag to anchor the protein-synthesis dependent long term enlargement of the spine. The structural correlate of L-LTP.

Tanaka, J., Horiike, Y., Matsuzaki, M., Miyazaki, T., Miyazaki, T., Ellis-Davies G.C.R. and Kasai, H. (2008) Protein synthesis and neurotrophin dependent structural plasticity of single dendritic spines. Science 319:1683-1687.

Harvery, C.D. & Svoboda, K. (2007) Locally dynamic synaptic learning rules in pyramidal neuron dendrites. Nature 450:1195-1200.

Matsuzaki, M., Honkura, N., Ellis-Davies G.C.R. and Kasai, H. (2004) Structural basis of long-term potentiation in single spine heads. Nature 429:761-765.

Frey, U. & Morris, R. G. (1998) Weak before strong: dissociating synaptic tagging and plasticity-factor accounts of late-LTP. Neuropharmacology 37, 545–552.