Aging is accompanied by a progressive decline in memory and cognitive function. Aging people also experience a deterioration of sleep quality and efficiency. Although it is widely acknowledged that sleep has a critical role in learning and memory, the link between age-related sleep disruption and memory deficits remains unclear. We have previously shown that learning-induced formation of new synaptic connections in the cortex represents structural changes correlated with long-term memory storage. Our preliminary data suggests that sleep promotes synapse formation and performance improvement after learning in young adult animals. Moreover, learning-induced synapse formation is reduced in the motor cortex of aged mice. Based on these findings, we hypothesize that age-related sleep impairment contributes to the reduction in learning-dependent synapse formation and behavioral improvement. In this application, we will test this hypothesis by combining in vivo imaging of synapse structure and function, recording and behavioral testing in the same animals. The proposal has two specific aims. In the first aim, we will examine the role of sleep in learning-dependent synapse remodeling and behavioral performance in young, middle-aged and old mice. This will test the hypothesis that the benefit of sleep in promoting synapse formation and memory encoding is diminished in older mice. In the second aim, we will use in vivo calcium imaging to determine whether sleep- dependent reactivation of task-related neurons is reduced in aging and whether such deficiency in sleep reactivation mediates learning-related synaptic deficits. The proposed project explores, for the first time, the role of sleep in age-related declie in learning and memory at the level of individual neurons and synapses in the living brain. Successful completion of the project will lay the foundation for future studies exploring the mechanisms by which sleep abnormalities contribute to cognitive dysfunction in neurological diseases such as Alzheimer's disease.

Public Health Relevance

Sleep disruption is frequently associated with cognitive dysfunction and memory loss in aging people. This project will use animal models to investigate the function of sleep in learning and memory at the level of individual neurons and synapses. Results from proposed project will provide important insights into synaptic mechanisms of sleep-dependent memory impairment in the aging brain, and suggest that improving sleep through effective interventions would enhance cognition and performance in older population.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Exploratory/Developmental Grants (R21)
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Aging Systems and Geriatrics Study Section (ASG)
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Mackiewicz, Miroslaw
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New York University
Schools of Medicine
New York
United States
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Cichon, Joseph; Blanck, Thomas J J; Gan, Wen-Biao et al. (2017) Activation of cortical somatostatin interneurons prevents the development of neuropathic pain. Nat Neurosci 20:1122-1132
Garré, Juan Mauricio; Silva, Hernandez Moura; Lafaille, Juan J et al. (2017) CX3CR1+ monocytes modulate learning and learning-dependent dendritic spine remodeling via TNF-?. Nat Med 23:714-722
Garré, Juan Mauricio; Yang, Guang; Bukauskas, Feliksas F et al. (2017) An Acute Mouse Spinal Cord Slice Preparation for Studying Glial Activation ex vivo. Bio Protoc 7:
Huang, Lianyan; Hayes, Scott; Yang, Guang (2017) Long-lasting behavioral effects in neonatal mice with multiple exposures to ketamine-xylazine anesthesia. Neurotoxicol Teratol 60:75-81
Wang, B; Liu, Y; Huang, L et al. (2017) A CNS-permeable Hsp90 inhibitor rescues synaptic dysfunction and memory loss in APP-overexpressing Alzheimer's mouse model via an HSF1-mediated mechanism. Mol Psychiatry 22:990-1001
Li, Wei; Ma, Lei; Yang, Guang et al. (2017) REM sleep selectively prunes and maintains new synapses in development and learning. Nat Neurosci 20:427-437
Ma, Lei; Qiao, Qian; Tsai, Jin-Wu et al. (2016) Experience-dependent plasticity of dendritic spines of layer 2/3 pyramidal neurons in the mouse cortex. Dev Neurobiol 76:277-286
Qiao, Qian; Ma, Lei; Li, Wei et al. (2016) Long-term stability of axonal boutons in the mouse barrel cortex. Dev Neurobiol 76:252-61
Huang, Lianyan; Cichon, Joseph; Ninan, Ipe et al. (2016) Post-anesthesia AMPA receptor potentiation prevents anesthesia-induced learning and synaptic deficits. Sci Transl Med 8:344ra85
Garré, Juan Mauricio; Yang, Guang; Bukauskas, Feliksas F et al. (2016) FGF-1 Triggers Pannexin-1 Hemichannel Opening in Spinal Astrocytes of Rodents and Promotes Inflammatory Responses in Acute Spinal Cord Slices. J Neurosci 36:4785-801