New Principal Investigators 12

During an early developmental period also known as the “critical period” (CP), cortical inhibitory networks are immature and passive exposures to environmental sounds readily shape the frequency tuning map of the primary auditory cortex (A1) (de Villers-Sidani et al., 2007). Maturation of cortical inhibition ultimately closes the CP, and early experience-dependent alterations in A1 tuning become consolidated and resistant to passive sound exposures. Moreover, a minimum inhibitory tone is necessary for the maintenance of this representational stability in the adult cortex (Pizzorusso et al., 2002).

In aged rats and humans, although learning is still possible, the process is usually slower and effects short-lived (Boyke et al., 2008; de Villers-Sidani et al., 2010). Notably, the inhibitory elements that are associated with the regulation of plasticity during early development are reduced in the aged brain (Caspary et al., 2008). This altered milieu could result in a progressive increase in representational instability in the aged A1, potentially contributing to the reduced effectiveness of learning in older individuals. Here we tested this hypothesis by comparing the effect of a short passive tone exposure on A1 frequency representation in young adult and aged rats. We found that such exposure resulted in a significant distortion of A1 frequency tuning in the older but not in the younger group. Additionally we found that such distortions could readily be erased by a subsequent exposure to a different tone. Finally we administered the GABA-A potentiator diazepam in the aged group during the exposure and found that it made A1 once again resistant to passive alterations in frequency tuning. Our findings show that experience-dependent plasticity is paradoxically enhanced but dysregulated in the aging brain likely due to an age-related reduction in inhibition. Such instability could impair the acquisition and persistence of learning in the aged brain.