Sunday, February 19, 2012

A Brain Zapping Method of Removing Unwanted Nerve Connections

Scientists at the University of Western Australia have devised an intriguing method of removing unwanted neural connections in mice. Whether or not this procedure is directly applicable to humans, it opens a world of possibilities for improving the mental lives of a wide range of persons at every stage of life, from early onset schizophrenia through the brain maladaptations of senescence.

One of the pillars of Aubrey de Grey's Sens approach to anti-ageing is the removal of malfunctioning cells in the body. There is an analogous need in the brains of many individuals to remove malfunctioning or excess nerves and nerve connections, to optimise or improve brain functioning. Here is more on the experiments in mouse brains:
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. _NewScientist
The brain is in a constant state of plasticity and re-shaping throughout life. But the brain often ends up in malfunctioning or maladaptive states which can be difficult to re-shape, without outside assistance. Part of the problem may lie in the genomics or gene expression of receptors or ion channels -- leading to consequent problems at higher levels of neuron function and the function of neuronal assemblies. Optimally, the underlying genetic or epigenetic cause would be corrected. But that isn't possible in most cases -- not yet.

In the meantime, workaround solutions such as the one discovered by the Australian researchers, may well allow for cruder fixes that can still add significantly to the quality of a person's mental existence.

The challenge in this case is to not only remove unwanted nerves or neural connections. One must also be able to stimulate growth of new neural connections in more optimal configurations.



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