- 8 February 2012 by Wendy Zukerman
ZAPPING the brain with a weak magnetic pulse can wipe out unwanted neural connections in mice at least. The discovery could be turned into a treatment for conditions associated with abnormal neural circuitry, such asschizophrenia.
In transcranial magnetic stimulation a magnetic coil induces electric currents in the brain that can strengthen or suppress neural connections. This technique has been shown to improve symptoms in people with brain disorders such as autism and depression.
Now, Jennifer Rodger from the University of Western Australia in Crawley and colleagues have found that stimulating the brain at intensities lower than would make a neuron fire can remove unwanted neural connections in mice.
As children, our brains produce too many connections between cells. As we develop, some connections are pruned away while others are strengthened. Inept pruning has been implicated in schizophrenia.
Rodger’s team used genetically modified mice with abnormal connections in an area of the brain called the superior colliculus (SC), which is involved in motion detection. In these mice, 90 per cent of the axons in the SC had extended into the wrong areas. These bad connections make it difficult for the rodents to follow moving objects in their line of sight.
Rodger used low-intensity, pulsed magnetic field stimulation (PMF) on the rodents’ SC for 10 minutes a day over two weeks. It is thought that PMF is too weak to make healthy neurons fire. But after treatment, tissue analysis showed that only 45 per cent of the abnormal axons were still there. “The axons that weren’t in the right place were wiped out,” says Rodger. After treatment the mice were also better at tracking objects.
“PMF is awakening unwanted connections, so the brain can detect and remove them,” says Rodger.
Unwanted neurons generally express high levels of a specific NMDA glutamate receptor. According to Rodger, this makes them sensitive to changes in electrical activity and so even low-intensity pulses can activate these neurons.
NMDA receptors send out signals that trigger the recruitment of two chemicals called nitric oxide and brain-derived neurotrophic factor (BDNF), which help remove abnormal circuitry in healthy brains. Indeed, modified mice given PMF expressed higher levels of both chemicals, while only minor changes were found in healthy mice or those given a sham procedure (The FASEB Journal, DOI: 10.1096/fj.11-194878).
“I think it is a very promising avenue for treatment of nervous system disorders that involve abnormally abundant and inaccurate connections,” says Rodger.
Perminder Sachdev at the University of New South Wales in Sydney, Australia, says it is “very exciting” and also surprising that low-power magnetic pulses can reverse a developmental disorder. But you can’t be sure normal circuits are not affected, he adds. “One cannot assume that these effects will always be positive.”