By Anna Tarasova ’19

Being able to form, maintain, and strengthen neural connections within the auditory cortex is an important part of language acquisition. Neural plasticity, or the ability of the brain to establish new connections, is especially high in childhood, but decreases with age. A discovery made by Dr. Jay Blundon and his colleagues at the St. Jude Children’s Research Hospital has the potential to restore auditory cortex plasticity well past childhood.

Changes in cortex plasticity are mediated by adenosine, a nucleoside that inhibits presynaptic neurotransmitter release and prevents long-term potentiation (LTP). LTP refers to the strengthening of neural connections through activity patterns – for example, remembering and responding to a sound after hearing it multiple times. The researchers hypothesized that blocking presynaptic adenosine receptors (A1Rs) would enable long-term potentiation in the auditory cortices of adult mice, thus increasing their plasticity to prior levels. The degree of plasticity was measured by mapping the neural response to an auditory stimulus. The team used three different gene-modifying mechanisms to deactivate A1Rs: injection of interfering RNA, conditional deletion, and crossing of two lines of mice to induce deletion. However, not all were effective in increasing plasticity. The most effective method was found to be inhibiting A1Rs pharmacologically with FR194921, an A1R antagonist. The researchers further solidified their finding with a “reverse experiment” – juvenile mice were treated with an A1R agonist and were found to have decreased auditory cortex plasticity. This suggests that the mechanism for a sudden decrease in plasticity as the mice near maturity is mediated by increased adenosine production.

Dr. Blundon’s findings have yet to be confirmed with human research participants. However, the discovery of the mechanism for auditory cortex plasticity can aid pharmaceutical chemists in formulating medication for people affected by neurodegenerative diseases that affect hearing. Furthermore, improving cortical plasticity in adults can be beneficial for tone discrimination, which is important in learning languages and musical skills. This implies that in the future, A1R inhibitors may enable older adults to learn new languages or enhance musical performance.

References:

1. J. Blundon et al., Restoring auditory cortex plasticity in adult mice by restricting thalamic adenosine signaling. Science 563, 1352-1356 (2017). doi: 10.1126/science.aaf4612.
2. Image retrieved from: https://upload.wikimedia.org/wikipedia/commons/thumb/e/ec/Auditory_Cortex_Frequency_Mapping.svg/800px-Auditory_Cortex_Frequency_Mapping.svg.png