Cognitive deficits, such as learning and memory impairments, are common in people subjected to chronic disturbance of the circadian cycle due to shift work, travel, or genetic dysregulation of the circadian clock. Epidemiological studies have revealed a global rise in cognitive disorders with circadian disruptions comorbidity such as autism, and Alzheimer’s disease, stressing the need to identify the causal relationship between these phenomena. However, the molecular mechanisms linking the circadian cycle and cognitive performance in health and disease remain largely unresolved. Neuronal synapses are the cellular basis for learning and memory processes. Synapse number, activity, and expression levels of synaptic proteins show rhythmic time-of-day- dependent changes, yet how these changes are regulated by the circadian clock is poorly understood. A growing body of work supports a critical role for the glial cells, astrocytes in normal clock function. Astrocytes are important synaptic regulators, and key for establishment and maintenance of memory and learning. In the mammalian cortex, the development of astrocytes and synapses coincide, where synapses begin to form only after astrocytes have been generated. Importantly, the rhythmic expression of molecular clock genes in the cortex follows similar developmental trajectory. This suggests the hypothesis, that correct establishment of synaptic connections and rhythmicity is linked to correct development of the circadian clock. Yet, how the astrocytic clock regulates synaptic rhythmicity and related cognitive performance has not been thoroughly examined. This critical gap in knowledge must be addressed in order to understand not only the fundamental functions of the astrocytic clock, but also to characterize the regulatory mechanisms that control circadian changes in synaptic levels. This supplemental application will define the role of astrocytic clocks in regulating the development of synapses, synaptic rhythmicity and subsequent learning and memory behaviors in two aims. Aim 1 investigates how early life perturbation of the astrocytic molecular clock located either in the SCN or peripheral brain regions (e.g., cortex, hippocampus) impacts astrocyte ability to support synapse formation. In Aim 2, we will determine how the developmental perturbations to the astrocytic clock impact time-of-day- dependent changes in synapses and cognitive performance in adulthood. Successful completion of these aims will uncover the role of astrocytic clock in regulating the establishment of synaptic and cognitive rhythms and reveal strategies for future manipulation of synaptic rhythmicity through astrocyte-targeting, to restore cognitive function in people suffering from neurological disorders.