Homeostatic control of hippocampal synaptic transmission

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In the hippocampus, a brain region involved in learning, memory, and spatial navigation, the ability of synaptic connections between neurons to undergo changes in strength shows circadian rhythmicity. This property of hippocampal synaptic plasticity suggests that the ability to form new memories similarly is regulated dynamically over the course of the day. The daily changes in hippocampal function correlate with cycling levels of hormones, such as melatonin and corticosteroids. This project examines how these hormones contribute to the circadian functionality of neurons, astrocytes, which constitute an important non-neuronal cell type in brain, and excitatory transmission at different sets of hippocampal synapses. Understanding these cellular and molecular mechanisms is crucial for understanding why and how memory formation is modulated across the course of the day. In addition to advancing knowledge of fundamental aspect of hippocampal function, this project provides inter-disciplinary research opportunities for undergraduate students, especially students from under-represented minorities. The project also includes public engagement as a core activity and allows for the trainees’ families and friends to learn about the research environment, thereby making a tangible impact on the lives of many first-generation college students. Numerous studies have identified the molecular underpinnings of different forms of neuronal plasticity, but much less is known about the plasticity of distinct types of glial cells that closely interact with neurons: astrocytes. Astrocytes undergo profound morphological changes in the hypothalamus during lactation, and a growing body of evidence indicates that astrocyte remodeling is much more common than previously thought. Their close proximity to synapses and abundant expression of neurotransmitter transporters allow astrocytes to powerfully control synaptic transmission and plasticity. Yet, there currently is limited knowledge of how these cells modulate excitatory synaptic transmission in the hippocampus, and how their modulation varies across the course of the day. The overall objectives of this project are to: (i) identify the molecular trigger(s) of neuron and astrocyte remodeling; and (ii) determine how these forms of remodeling shape synaptic transmission at different sets of synapses. The central hypothesis is that astrocyte remodeling changes the weight of proximal versus distal excitatory inputs in CA1 pyramidal cells. Identification of the molecular mechanisms that underlie circadian regulation of synaptic transmission and plasticity in the hippocampus and, in particular, the role that astrocytic cells play therein, will advance understanding of the complex mechanisms through which brain activity is modulated by non-neuronal cells.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.