Tohoku University Graduate School of Life Sciences

Laboratory of Molecular and Cellular Neurosciences

 

　

By the last earthquake and tsunami, the north-east Japan including Sendai city has severely damaged.  We are very grateful to the inquiries and supports from you.  However, the damage was minimum in our laboratory and the laboratory members and their families are all safe.  The facilities such as water supply and electricity were already recovered.  The gas line will be recovered in this March.  The traffic and transport are now recovering.  It is expected that we will restart our educational and research program in this April. (2011/3/23)

　

　

　

　

　

Brain is one of miracles produced by living organisms and is wrapped in mystery.  It is functionally diverse and complex, but is not chaotic.  Some principles are suspected to be present in the brain function.  In the brain, neural information is carried from neuron to neuron at the synapses, where bouton-like terminals of axon attaches dendritic neuronal processes.  A single neuron typically has hundreds to thousands of synapses.  The activity of a neuron is thus determined by the integration of synaptic activities, some of which are excitatory and others that are inhibitory.  Brain functions such as learning and memory are explained by the plastic change of synapses.  We are revealing the molecular mechanisms how the organism’s environments and experiences affect the morphology and the function of synapses (synaptic plasticity). 

The hippocampus is clearly involved in the normal formation of long-term declarative memory.  Functional imaging of the normal human brain shows that the hippocampus is activated during certain kinds of memory tasks.  Bilateral damage to the hippocampus results in an inability to form new declarative memories.  The hippocampal mossy fiber axons arise from the granule cells of the dentate gyrus and form exceptionally large excitatory synapses on the proximal dendrites of CA3 pyramidal cells.  Because of this particular organization, dynamic changes in their synaptic strength are thought to exert a dominant influence over information processing in the hippocampus.

There are many unrevealed problems on the plasticity of presynaptic terminals.  How the transmitter release is regulated?  How is morphological malleability of presynaptic terminals regulated?  Are morphologically new synapses all functional?  How a synapse become functional?  What is the retrograde signals from dendrites to presynaptic terminals?  How is the neurogenesis regulated in the hippocampus?  How does the newly generated neuron form synapses on its targets?

Despite the importance of synapses, there remains a vast unexplored field in the physiology of presynaptic terminals.  The progress of research is hampered by three major difficulties: (1) the small size of presynaptic terminals that are typically 0.5-2 μm, (2) the functional heterogeneity and (3) the biochemical complexity of presynaptic functions.  We plan to overcome these difficulties by problem-oriented approaches focused on the hippocampal mossy fiber synapses (Fig. 1), using molecular-biological, cell-biological, physiological and ethological methods in concert.  We are investigating above problems using brain slices and slice cultures.  New physiological methods are developed to quantify various presynaptic functions.  The Ca²⁺ dynamics is measured from the individual mossy fiber terminal by introducing Ca²⁺-sensitive dextrans in the presynaptic terminal (Fig. 2).  We have found that functionally diverse Ca²⁺ channel subtypes make the individual presynaptic terminal unique.  Such synaptic individuality at the molecular level is speculated to be a mechanism of brains’ complexity and fluidity.  We are visualizing the functions of individual presynaptic terminals by designing derivatives of fluorescent proteins and by introducing them using viral vectors.  The synaptic vesicle is pH 5 inside whereas it becomes pH 7.4 after exocytotic fusion with plasma membrane.  The pH-sensitive GFP derivative was attached to the C-terminus of a synaptic vesicle protein, synaptobrevin/VAMP so as to sense pH inside the vesicle (Fig. 3). 

In the adult hippocampus neuronal progenitor cells differentiate to new neurons and form novel networks (Fig. 4).  We developed a slice culture system that enables us to quantify the hippocampal neurogenesis.  We are investigating how neuronal damage is compensated by newly differentiated neurons

              From a tiny window of the mossy fiber synapse, you would be able to see the brain and to realize the human beings.

 

 

 

PROFESSOR

              Hiromu YAWO, Cellular and Developmental Neurosciences, Physiology of Synapse      [Publications]

 

ASSOCIATE PROFESSOR

              Toru Ishizuka, Ｍolecular Neuroscience