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Takao Hensch (l) and Eun-Jin Yang

Behavioral preferences are shaped from an early age and often last a lifetime. Even before they are 1 week old, babies prefer hearing their mother’s voice over that of others or their native tongue over a foreign one. Detailed animal studies have unraveled mechanisms of circuit refinement in primary sensory areas that determine windows of early development when the sculpting hand of experience is most potent. Very little is known, however, about such critical periods underlying higher order brain functions like behavioral preferences.

For instance, humans exposed to a certain type of music in youth are likely to seek out that music in adulthood—but what about mice, a well established model organism in biological studies? In a recent paper published in PNAS, postdoctoral fellow Eun-Jin Yang and recent Harvard College alumnus Eric Lin (’12) in the laboratory of Professor Takao Hensch employed a novel version of nesting behavior assay to confirm the existence of a critical period for acoustic preference in standard C57BL/6 lab mice. Early exposure to classical music or jazz, between postnatal days 15 and 24, reversed the mouse’s natural bias for silent shelter. Then, researchers turned to a pharmacologic means, using valproic acid, a histone deacetylase inhibitor and a genetic approach, deleting Nogo receptor, to successfully re-open this higher order critical period in mouse adulthood. Such manipulations were designed to release key molecular “brakes” on brain plasticity first identified in the primary visual cortex by disrupting epigenetic factors or structural cues like myelin signaling.

Visualizing neurons activated by the heard music with an immediate early gene, cFos, the team found that the medial prefrontal cortex (mPFC) was significantly more engaged during open periods of plasticity for acoustic preference than when the critical period was closed. This mPFC involvement in establishing behavioral preference is not surprising, considering that the mPFC is known to regulate complex brain functions like working memory, attention, and gating emotion. Since music is thought to reduce anxiety under certain circumstances, the shifts in musical preference were also studied in relation to the amount of time mice crossed the center of an open field testing arena, a classic measure of anxiety in rodents. Strikingly, the results suggested that the mice might have been experiencing less anxiety during the re-opened periods of plasticity.

In a companion paper (Weikum et al, PNAS, in press), Hensch and his collaborators at the University of British Columbia reveal that the timing of critical periods for phoneme discrimination in human infants is similarly sensitive to drug exposure such as to antidepressants. Studying acoustic preference in mice not only offers insights into the regulation of higher order critical periods in general but also paves fascinating new ways to obtain clues about the plasticity of brain circuits governing emotional states in human.


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