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- Our current research and education are focused on the neural functions of cerebral cortex and limbic brain (hippocampus, amygdala, etc.) using techniques of neuroanatomy, electrophysiology, biochemistry and behavioral neuroscience. Major topics are (1) the mechanisms for information processing in the neuronal circuits by analyzing the synaptic structure and function, (2) a mechanism for signal transduction in the cerebral cortex and limbic system, and (3) a mechanism for learning and memory through synaptic potentiation and efficiency control.
- To study the neural activity and the neuronal plasticity observed during animal behaviors depending on its experiences, it is required to perform multi-faceted research covering extensive fields, ranging from molecules to behaviors. At our laboratory, we are attempting to achieve this goal by taking single-cell recordings from the brains of behaving animals, making use of patch clamping in vivo.
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The synaptic contacts are composed of cell adhesion and extracellular matrix molecules (CAMs and ECMs) which are sensitive to intracellular and extracellular signaling. It has been unveiled that proteases cleaving CAMs and ECMs and the cleaving process might regulate the synaptic potentiation relating cortical and limbic brain functions. In our laboratory, several novel secretory-type serine proteases were cloned and we have analyzed their functions in detail. To date, we have demonstrated that neuropsin (also referred to as klk8) plays a significant role in the regulation of E-LTP (early phase of long-term potentiation), and regulates intracellular signals of the limbic brain. However, there are many unresolved questions over how this protease affects the signals from outside into inside of the cells and how it regulates the synaptic function via proteolysis processing. Moreover, it is unknown what roles this mechanism plays in acquisition and/or retention of memories. Current our research is in progress to resolve these questions on molecular mechanisms of behavioral memory.
With the goal of clarifying the relationship between these diverse molecules and activity-dependent neuronal plasticity, we are conducting analyses with advanced techniques (e.g., use of transgene animals and in vivo local modification of genes carryed by virus vectors). For example, we recorded and analyzed sensory and motor-related information in individual animals by a “selective patch clamp recording” called two-photon targeted patching, from nerve cells infected an expression vector with a modified gene. This is expected to allow direct investigation of information processing in individual brains and molecular mechanisms for neural plasticity during information processing. In other words, one major research topic for us is “comprehensive understanding of brain functions by relating the functions of particular molecules in particular nerve cells (ion channel, protease, cell adhesion molecule, neurotrophic factor, etc.) to the behaviors of individuals.”
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- Komai S et al., Nature Protocols, 1, 629-634, 2006
- Nakamura Y et al., J. Cell Sci., 119, 1341-1349, 2006
- Tamura H et al., J. Physiol., 570, 541-551, 2006
- Matsumoto-Miyai K et al., J. Neurosci., 23, 7727-7736, 2003
- Shiosaka S, ISI Highly Cited Researchers
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Fig. 1 Electron microscopic profile of a synapse in the hippocampal pyramidal layer. Presynapse is colored green and postsynapse is blue.
Fig. 2 Electrophysiological analysis of synaptic functions. Electrodes are inserted into the hippocampal slice and membrane currents or potentials are recorded.
Fig. 3 Behavioral analysis of memory and learning. Animals (mice) are given various learning tasks and the course of their learning is observed in detail.
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