Project Summary
Despite the overall reduced responsiveness to external stimuli during sleep, incoming sounds are processed
by a highly active and broadly projecting auditory system. Moreover, not only the acoustic aspects of sounds
are processed during sleep but also their associated meaning, as evidenced by a higher likelihood of
awakening from novel and meaningful sounds as compared to familiar and meaningless sounds. These and
other findings suggest that there is ongoing semantic neural processing during sleep, yet the underlying brain
circuits and neurophysiological mechanisms remain poorly understood. Sound salience processing during
sleep enables rapid arousal when a behavioral response is appropriate, such as in the presence of danger or
when an infant is in need. However, as millions of people in the US and worldwide live in noisy urban
environments, in which they are exposed to household, traffic and other neighborhood sounds during sleep,
ongoing processing of sounds during sleep may come at a cost. During sleep in the absence of incoming
sounds, brain circuits engage in internally generated neural activity patterns that underlie memory
consolidation–the transformation of temporary and labile memory traces into long-term memories. A potential
interaction between sound processing and memory processes during sleep has been proposed by recent
epidemiological studies which link exposure to nighttime noise and memory impairments. Moreover, we have
recently discovered that acute exposure to non-awakening sounds during sleep impairs subsequent memory
retention in rodents. However, the acoustic properties of sounds impairing memory consolidation, the
consequences of chronic exposure to sounds during sleep on memory capacities and the neural interactions
between online sound processing with offline neurophysiological signatures of memory consolidation are
largely unknown.
We will fill these knowledge gaps using electrophysiological and optical recordings from multiple brain regions,
closed-loop sound manipulations and light-activated modulation of neural activity in freely behaving and
naturally sleeping mice. In Aim 1, we will determine the role of key brain regions in sound salience processing
during wakefulness–the auditory cortex and ventral tegmental area–in processing of sound salience during
sleep. In Aim 2, we will determine the acoustic properties of sounds that impair memory processes and the
consequences of chronic sound exposure during sleep on memory capacities. In Aim 3, we will determine the
acute and chronic consequences of sound processing during sleep on circuit-level neurophysiological
mechanisms of memory consolidation. Together, these experiments will provide a mechanistic understanding
of the neuronal substrates underlying sound processing during sleep and their mnemonic consequences.