Amar Sahay, PhD
Harvard Medical School
Broad Institute of MIT and Harvard
The incidence and complexity of mental illnesses and cognitive impairments associated with ageing and Alzheimer’s disease underscores the need to develop novel treatments. Our mission is to generate fundamental insights into the role of adult hippocampal neurogenesis, the process by which neural stem cells generate dentate granule neurons throughout life, in hippocampal functions in encoding, memory processing and modulation of mood. By integrating cellular, circuit, systems and behavioral interrogation of adult hippocampal neurogenesis, we aspire to rejuvenate and re-engineer hippocampal circuitry to optimize circuit performance in diseases such as depression, anxiety disorders, Alzheimer’s disease and ageing.
To address this goal, we have established a multifaceted research program that integrates inducible mouse- and viral-genetics, pharmaco- and optogenetics, synaptic tracing, ex vivo slice physiology, in vivo awake behaving optical imaging, 2 photon imaging, human cellular reprogramming, and behavioral analysis. Specifically, we are interested in the following questions.
1. How are neural stem cell activation-quiescence decisions physiologically regulated?
2. What are the mechanisms underlying lineage homeostasis and experience dependent integration of adult-born neurons?
3. How do properties and connectivity of adult-born neurons causally relate to their encoding and memory functions?
4. How does adult hippocampal neurogenesis influence hippocampal activity and limbic circuits sub serving mood?
5. How do our studies on properties and connectivity of adult-born neurons in rodents inform our thinking of the human brain in health and disease? 6. What are the molecular mechanisms operational in the hippocampus underlying resilience and vulnerability to stress?
NIH Director discusses our recent study on memory precision and aging in Nature Medicine (https://directorsblog.nih.gov/2018/05/24/unlocking-the-brains-memory-retrieval-system/)
Recent review on the functions of adult-born neurons in memory processing in Nature Neuroscience (https://www.nature.com/articles/s41593-019-0484-2)
Review on "Communication, cross talk and signal integration in the adult hippocampal neurogenic niche” (Neuron 2020)