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Ksenia Kastanenka, PhD




Assistant Professor




Assistant Professor




Yee Fun Lee1,2, Alyssa N. Russ1, Qiuchen Zhao1, Megi Maci1, Morgan R. Miller1, Steven S. Hou1, Moustafa Algamal1, Alfonso Araque3, Elena Galea4,5,6, Brian J. Bacskai1, Ksenia V. Kastanenka1

Optogenetic Targeting of Astrocytes Restores Sleep-Dependent Brain Rhythm Function and Slows Alzheimer’s Disease

I am an Assistant Professor of Neurology at Massachusetts General Hospital and HMS. My research program is focused on Alzheimer’s disease. I have over 15 years of experience studying neuronal circuits. I have served as a PI on multiple research grants and have experience leading a research team. We use state of the art laboratory techniques, including optogenetics and multiphoton microscopy to dissect the role sleep-dependent brain rhythms play in etiology and progression of Alzheimer’s disease. It is important to participate in the Women in Medicine and Science Symposium to disseminate our work and also to support other women scientists.


Patients with Alzheimer’s disease (AD) exhibit sleep disturbances, specifically deficits in deep non-rapid eye movement (NREM) sleep. Disruption of NREM slow waves occurs early in the disease progression and is recapitulated in transgenic mouse models of beta-amyloidosis. However, the mechanisms underlying slow-wave disruptions remain unknown. Also, it is not clear if these sleep disturbances are a cause or effect of AD. Because astrocytes contribute to slow-wave activity, we used multiphoton microscopy and optogenetics to investigate whether they contribute to slow-wave disruptions in APP mice. We monitored astrocytic calcium transients expressing genetically encoded calcium reporter Yellow Cameleon 3.6 (YC3.6) using multiphoton microscopy. The power but not the frequency of astrocytic calcium transients associated with slow waves was reduced. Optogenetic activation of astrocytes at the endogenous frequency of slow waves restored slow-wave power, reduced amyloid deposition, prevented neuronal calcium elevations, and improved memory performance. Our findings revealed malfunction of the astrocytic network driving slow-wave disruptions. Thus, targeting astrocytes to restore circuit activity underlying sleep and memory disruptions in AD could ameliorate disease progression.

Keywords: Optogenetics, astrocytes, sleep, slow oscillations, Alzheimer’s disease, multiphoton imaging, neuroinflammation, memory consolidation, calcium

This work was supported by the BrightFocus Foundation Grant A2020833S; the Alzheimer’s Association Grant AARG-18-52336; National Institutes of Health Grant R01AG066171.