The role of adult born neurons during sleep

In contrast to other brain regions in which neurogenesis is terminated at adulthood, the dentate gyrus of the hippocampus continues to generate new neurons across the human lifespan (Eriksson et al., Nat. Med., 1998). Several lines of evidence indicate that adult-born neurons can be used to regenerate damaged brain tissue (Sakaguchi and Okano, Dev. Neurobiol., 2012). To utilize adult-born neurons in clinical settings, it is essential to understand how new neurons integrate into existing neuronal circuits. We are the first to provide evidence that adult-born neurons are functionally incorporated into neuronal circuits encoding new memories (Arruda-Carvalho* and Sakaguchi* et al., J. Neurosci., 2011, *equal contribution).


Previous studies suggest that sleep is important for memory formation (e.g., Maquet, Science, 2001). For example, neurons that are activated during learning are re-activated during sleep (e.g., Wilson and McNaughton, Science, 1994). This reactivation is thought to be responsible for memory consolidation. However, evidence that adult-born neurons participate in memory formation during specific stages of sleep is lacking. In rodents, each sleep episode is very short in duration, (e.g., REM occurs for 60 seconds on average), making sleep stage-specific investigation of the function of adult-born neurons technically challenging.

Our group aims to overcome these challenges by utilizing the advanced techniques of  optogenetics to manipulate adult-born neurons during specific stage of sleep. Our goal is to clarify the mechanisms by which adult-born neurons incorporate into memory circuits during sleep, which could contribute to the prevention or treatment of neurodegenerative diseases.



Mechanism of Post-Traumatic Stress Disorder

Some memories are best forgotten. A traumatic memory can sometimes have a life-long effect on the thinking, emotions, and actions of people with post-traumatic stress disorder (PTSD). About 8 million people have PTSD in a given year, including war veterans, children, and those who have been assaulted, abused, survived an accident or disaster, or experienced other traumatic life events. Our brains temporally hold new memories while we are awake and later remember them while we sleep. This processing may be critical for remembering important memories for long periods of time or forgetting unnecessary memories.


PTSD is a condition that involves problems in memory processing. The symptoms of PTSD often include nightmares to an extent that sleep is frequently disturbed, which could lead to a malfunction in memory processing. Therefore, investigating how memories are processed during sleep is critical for understanding the pathology of PTSD and developing a cure.


In our current research, we are using optogenetics to examine how entire brain networks participate in memory processing during specific stages of sleep. We are also analyzing the metabolites that are involved in memory processing to identify a drug target that could be used to cure PTSD.