You can’t teach an old dog new tricks—or can you? Textbooks tell us that early infancy offers a narrow window of opportunity during which sensory experience shapes the way neuronal circuits wire up. A lack of proper stimulation during this “critical period” has a permanent and detrimental effect on brain development.
But new research shows the auditory system in the adult mouse brain can be induced to revert to an immature state similar to that in early infancy, improving the animals’ ability to learn new sounds. The findings, published Thursday in Science, suggest potential new ways of restoring brain function in human patients with neurological diseases—and of improving adults’ ability to learn languages and musical instruments.
In mice, a critical period occurs during which neurons in a portion of the brain’s wrinkled outer surface, the cortex, are highly sensitized to processing sound. This state of plasticity allows them to strengthen certain connections within brain circuits, fine-tuning their auditory responses and enhancing their ability to discriminate between different tones. In humans, a comparable critical period may mark the beginning of language acquisition. But heightened plasticity declines rapidly, and this continues throughout life, making it increasingly difficult to learn.
In 2011 Jay Blundon, a developmental neurobiologist at Saint Jude Children’s Research Hospital, and his colleagues reported that the critical periods for circuits connecting the auditory cortex and the thalamus occur at about the same time. (The thalamus relays information from the sense organs to the appropriate cortical area). These developmental windows seem to be controlled by a molecule called adenosine, levels of which rise after the critical period closes. This inhibits communication between cells in the two regions.
In the latest study the researchers wanted to determine if halting adenosine signaling would reinstate plasticity in the auditory cortex. In one set of experiments they used microelectrodes to measure how neurons in the auditory cortex of healthy adult mice responded to pure tones. Responses were compared with those from animals genetically engineered to lack the cell surface receptor to which adenosine binds. The analysis revealed cells in the auditory cortex of mice lacking the adenosine receptor responded to a larger range of frequencies than those of the wild-type mice.
To investigate further, Blundon and his colleagues inhibited adenosine signaling in several other ways. They engineered their own strain of mice, whose adenosine receptors could be deleted from thalamus cells when the mice reached maturity. The thalamus sends fibers to the area of the cortex where sounds are processed. This genetic engineering expanded the frequency of sounds to which cells in the auditory cortex were responsive, improving the mice’s perception of the sounds and improving their ability to discriminate between similar tones. Blocking adenosine signaling with a drug had the same effect on healthy mice. “This [signaling] mechanism, if blocked, is sufficient to extend critical plasticity to late adulthood,” says developmental neurobiologist Stanislav Zakharenko, senior author of the study, adding that the findings could help to make language learning in adults more efficient. “Learning a language is very easy for two- to three-year-olds, but language learning courses for adults aren’t very effective, even though adults are still capable of learning other skills effectively,” he says. “But if I take a take a language course while inhibiting adenosine production or signaling in the thalamus, I would acquire the information quicker, retain it for longer and maybe lose my accent.”
The researchers also believe their findings could offer a new treatment for conditions such as stroke as well as tinnitus, or ringing in the ears. They think drug that blocks adenosine signaling could circumvent stroke damage to the auditory cortex by restoring plasticity, and by “retraining” healthy surrounding areas to respond to sounds normally processed by the damaged areas.
Not everyone is convinced by the results, however. “The range of techniques deployed in this work is very impressive,” says neuroscientist Jennifer Linden of the Ear Institute at University College London who was not part of the study. “[But] I am skeptical about the conclusion that disrupting adenosine signaling in the thalamus rejuvenates plasticity in the auditory cortex and improves auditory perception.” She says interfering with adenosine signaling could alter the excitability of neurons in the thalamus. That would make it unclear whether the observed changes in plasticity and hearing arise specifically from inhibited adenosine signaling, rather than because of altered activity of another internal cell pathway in the thalamus.
Investigating this question is important because altering the excitability of thalamus neurons might impair auditory perception, Linden adds. “Decades of research have linked increased excitability in auditory brain structures with phantom sound perception in tinnitus,” she says. “If disrupting adenosine signaling produces improvements in cortical plasticity but also hearing problems such as tinnitus, then it would not be an effective means of improving auditory perception in humans.”
But Blunden and his colleagues stand by their assertions. Increased adenosine, he says, reduces the release of the signaling molecule glutamate in the thalamus, which in turn diminishes the activity of neurons in the auditory cortex. “That decrease in adenosine signaling is sufficient to restore cortical plasticity in adults, while activation of adenosine receptors in juveniles is sufficient to block it,” Blunden explains. “We do not claim that other processes that could conceivably alter thalamic excitability have no role in the presence or absence of adult auditory cortex plasticity or changes in auditory perception—though we know of no such processes that have been described, and have ruled some out in our previous publications.”
via Scientific American: Mind & Brain http://ift.tt/n8vNiX