Synapse Biology Unit (Yukiko Goda)

The human brain contains about 100 billion neurons, each receiving tens of thousands of synapses from other neurons to form a vast synaptic network that underlies brain functions from computation and perception to learning and memory. Synapse Biology Unit studies how the dynamic features of synaptic connections are realized and how they implement efficient information processing. Synaptic communication involves not only the interaction between the presynaptic and the postsynaptic sides of individual synapses, but interactions with nearby synapses and with the astrocyte network. We seek to understand the local synaptic circuit architecture that defines a functional unit underlying learning and memory. We also address the molecular and cellular basis of homeostatic mechanisms that balance various physiological changes and counteract pathological insults to facilitate maintenance of synaptic circuits over individual’s lifetime.

Within the above overall framework, we address several lines of research questions using cutting-edge imaging techniques and electrophysiology in combination with molecular genetic tools, biochemistry, proteomic and transcriptomic analysis methods. While most of our projects make use of the mouse hippocampus, the relevance of synaptic circuit dysfunctions in human brain disorders is explored through human iPS cell-derived neurons and astrocytes.

Heterosynaptic crosstalk of tripartite synapses

Synapses are highly diverse in shape and function. Even on a single pyramidal neuron, the many thousands of synapses on its dendritic tree display variable strengths. Such heterogeneity in synaptic strengths influence how dendrites integrate incoming synaptic information. Using hippocampal networks, we study how the discreteness of information flow and the efficacy of synaptic inputs received by single neurons are regulated with activity imposed in different ways in vitro, in vivo or by manipulating behavioral states, and the contribution of astrocyte network to such regulation (see below). We also examine how dysregulation of synaptic networks, particularly of functional properties of tripartite synapses are associated with neurodevelopmental and neurodegenerative brain disorders.

Organization of astrocytes in synaptic networks

In the brain, glial cells are just as numerous as neurons, and astrocytes are the most abundant glial cell type. Although astrocytes crucially contribute to a variety of brain functions by direct and indirect influences on neural circuit activity, the various astrocyte signaling modes and when and how they interface with the neural network remain to be clarified. To delineate the basis by which astrocytes and synapses interact to control information processing, consideration of the 3-D organization of astrocytes with respect to the local synaptic network, along with a better understanding of astrocyte cell biology particularly at the very fine processes that form the tripartite junctions, are warranted. We are exploring how the unique shape of astrocytes arise, how astrocytes are embedded in the highly organized hippocampal structure, and how astrocytes via their elaborate processes coordinate synaptic activity to shape physiological circuit functions.