Grown-Up Connections: Mice, monkeys remake brain links as adults

Two new studies raise the bar on estimates of the magnitude of changes in nerve connections in the brain’s outer layer, or cortex, during adulthood. Cells’ anchor points for these neural connections undergo substantial adjustments in the absence of training, scientists say.

Both reports, one on mice and the other on monkeys, appear in the March 16 Neuron.

The first investigation, directed by neuroscientist Karel Svoboda of Cold Spring Harbor (N.Y.) Laboratory, examined 27 adult mice that had been genetically modified to produce a cell-labeling substance. The label enabled researchers to obtain images of message-bearing cell extensions, or axons, in the cortex. The imaging relied on a technique that uses infrared light to penetrate deep into the brain. The team probed each animal’s axons every 4 days, over periods ranging from 24 days to 9 months. The animals received no training during the experiment.

The overall structure, length, and number of axons in the animals’ brains remained largely stable, Svoboda’s team reports.

However, when the scientists examined synapses, the connections where nerve cells pass signals, cortical axons lost old synapses and formed new ones at greatly varying rates.

Axons that branched up from the thalamus, below the cortex, incurred few synaptic losses or gains. In contrast, axons that originated in nearby cortical regions displayed dramatic synaptic changes. In one cortical-axon group, one-fifth of the synapses that the researchers tracked had been replaced after 1 week. That proportion reached one-half after a month and about three-quarters by 9 months.

The entire population of synapses connected to certain groups of axons gets replaced many times during an animal’s life, Svoboda and his colleagues propose.

“Nothing could have prepared us for the prodigious rate of turnover” of synapses on those axons, remarks neuroscientist Edward M. Callaway of the Salk Institute for Biological Studies in La Jolla, Calif.

In the second study, a group led by neuroscientist Charles D. Gilbert of Rockefeller University in New York City used the same synapse-imaging technique to examine the gateway for visual information in the cortexes of two adult macaque monkeys for 2 weeks.

Researchers have long regarded this brain area, the primary visual cortex, as relatively resistant to change. However, axons in this area lost synapses at a weekly rate of about 7 percent and formed new ones at a comparable pace, Gilbert and his coworkers report.

They have yet to determine whether synaptic turnover occurs more frequently in certain classes of monkey axons. The rate of synaptic losses and gains on these axons probably rises further as adult monkeys learn various perceptual tasks, the scientists propose. The monkeys in the study had received no perceptual training.

Both new investigations build on mouse studies, also conducted by Svoboda’s group, finding that dendritic spines—which receive messages from axons across synapses—come and go at a rapid clip, 30 percent replacement each month.

It will take further work to determine whether cortical cells with high rates of synaptic turnover orchestrate flexible adaptations to an animal’s changing environment, Callaway says.