19 December 2002. Dendritic spines-tiny protrusions that mediate synaptic contacts between neurons-are present in vast numbers in the mammalian brain (up to ten thousand per neuron). For this reason, spine growth and retraction could hold the key to the making and breaking of neuronal connections that are thought to be essential for learning and memory. So just how stable are these spines? Two reports in today's Nature provide quite different answers.
Both papers describe the use of transgenic mice to image, in vivo, spines expressing fluorescent proteins. In work directed by Karel Svoboda, Cold Spring Harbor Laboratory, Long Island, New York, first authors Joshua Trachtenberg and Brian Chen, together with colleagues at the University of Lausanne, Switzerland, and Washington University, St. Louis, used green fluorescent protein to track the appearance and disappearance of spines in the barrel cortex of young adult mice. Trachtenberg et al. found three types of spines-transient, semistable, and stable-which appeared to last about one day, two-three days, and longer than eight days, respectively. About 20 percent of spines were transient, while about 50 percent were stable. Even the latter, however, were found to turn over, with a projected half-life of about 120 days.
Trachtenberg et al. also demonstrate, using the electron microscope, that the waxing and waning of spines is accompanied by synapse formation and loss, suggesting that spine turnover is functionally significant. In support of this, the authors found that sensory perception could influence the turnover of spines. To investigate this possibility, Trachtenberg et al. first determined which neurons in the barrel cortex were stimulated by tweaking specific whiskers. They then plucked, chessboard fashion, selected whiskers from one side of the face only, and found that spine turnover increased by almost 50 percent in corresponding neurons. Dendrites associated with the intact whiskers showed no change in spine dynamics.
In a remarkably similar approach, researchers in Wen-Biao Gan's lab at New York University used transgenic mice expressing yellow fluorescent protein to reveal, surprisingly, a totally different dynamic in the primary visual cortex of one-month-old mice. Jaime Grutzendler et al. found that spines in this region of the brain are extremely stable. At most, six percent of spines appear to turn over within three days, and 27 percent over a month. At four months of age, spines were even more stable. In these animals, 96 percent of spines remained unchanged after a month; spine half-life was calculated to be just over one year.
Why these two groups should obtain such different results is unclear, write Ole Ottersen and Johannes Helm, University of Olso, in a companion news and views article. They suggest that the different cortical regions selected for study-barrel vs. visual cortex-may offer some explanation, and they conclude that these first successful attempts at imaging live spines should provide the necessary impetus for further experimentation.-Tom Fagan.
Trachtenberg JT, Chen BE, Knott GW, Feng G, Sanes JR, Welker E, Svoboda K. Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex. Nature 2002 December 19/26;420:788-794. Abstract
Grutzendler J, Kasthuri N, Gan W-B. Long-term dendritic spine stability in the adult cortex. Nature 2002 December 19/26;420:812-816. Abstract
Ottersen OP, Helm, PJ. How hardwired is the brain? Nature 2002 December 19/26;420:751-752. Abstract