シナプス生物学ユニット(合田 裕紀子)

Overview

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. The Synapse Biology Unit studies how the dynamic features of synaptic connections are realized, and how they mediate and maintain efficacious 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 synaptic circuit architecture that defines the minimal functional unit of synaptic functions underlying learning and memory in the rodent hippocampus. We also aim to delineate the molecular and cellular basis of homeostatic maintenance of synaptic circuits that serves to balance the physiological changes and counteract pathological insults.

Within the above overall framework, we address two major lines of research questions using cutting edge microscopy and techniques of electrophysiology in combination with molecular genetic tools, biochemistry, histology and transcriptomic analysis methods.

1.  Heterosynaptic crosstalk and synaptic plasticity

Synapses are highly diverse in shape and function. Even on a single pyramidal neuron, thousands of synapses that are typically formed on its dendritic tree display variable strengths. Such heterogeneity in synaptic strengths influence how dendrites integrate incoming synaptic information. In our recent work, we find that long-term potentiation (LTP) – a cellular correlate of memory – results in plasticity not only at the stimulated synapses but also at neighboring synapses whose direction of change is distance-dependent (Letellier et al., 2019; Tong et al., 2021). Such spread of plasticity raises the question of whether and how separate learning events are represented along the dendrite. Using hippocampal networks, we study how the discreteness of information flow of individual inputs are tuned, and if alterations in its regulation might lead to memory dysfunction. We examine also how heterosynaptic interactions control homeostatic adaptations associated with changes in brain states.

2.  Cellular and molecular control of reciprocal interactions at tripartite synapses

In the brain, glial cells are just as numerous as neurons, and astrocytes are the most abundant glial cell type. Although recent studies have increasingly established that astrocytes crucially contribute to a variety of brain functions by directly influencing neural circuit activity, our understanding of astrocyte signaling and how they interface with the neural network are still fragmentary. To delineate how astrocytes and synapses interact to control information processing, a better understanding of astrocyte cell biology, particularly at the very fine processes that form the tripartite junctions with neuronal synapses are warranted. We study the molecular components and mechanisms of activity-dependent signaling at the tripartite synapse, how astrocyte interactions coordinate the heterosynaptic crosstalk, and shape physiological circuit functions.

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