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Research

Fig.1 Integrative approach to understand neural circuit function

Brain is composed of over 100 billions of neurons. Neurons are highly differentiated in their morphological and biophysical properties. Furthermore, they are interconnected with each other via synapses, thus creating complex neural circuits. Recent advances in neuroscience give us a wealth of knowledge on the anatomical basis of neural circuits and also the properties of individual neurons and synapses. However, how these features actually shape a specific function of neural circuits is not well understood. We are addressing this question by using various techniques of electrophysiology, optics, morphology, molecular biology, and computations depending on the purpose of experiments (Fig.1). We currently have two core projects.

Neural mechanisms of sound localization

Fig.2 Sound localization circuit in brainstem

Our main research subject is mechanisms of sound localization. Sound localization is a behavior to identify the direction of sounds and requires detecting a difference in sound arrival times between the two ears (Fig.2). We can resolve as small as 1 degree of sound source changes along the horizontal plane, which corresponds to 10 microseconds of interaural time difference. This resolution of time is outstanding, considering that action potentials often have duration in the order of a millisecond in the brain. We are interested in how such a small time difference is extracted by binaural coincidence detector neurons in a brainstem circuit, and have studied their signal integration mechanisms using chicken brain slices. We are also interested in mechanisms how thus extracted binaural information is processed at higher order nuclei to create an auditory space map in the brain.

Structural plasticity at the axonal trigger zone

Fig.3 Axon initial segment plasticity after hearing loss

Axon initial segment (AIS) is a highly specialized neuronal structure that separates axonal and somatodendritic compartments. AIS is enriched with voltage-gated Na channels, and plays a critical role in initiating action potentials. We showed in brainstem auditory neurons that deprivation auditory nerve activity increased the length of AIS, thereby enhancing the excitability of the neurons (Fig.3). This indicates that AIS is highly plastic and changes its structure to regulate neuronal activity. Neural activity is crucial for the maintenance of neural circuit. Thus, this reorganization of AIS may work as a homeostatic mechanism to compensate for the loss of auditory nerve activity, thereby contributing to the maintenance of auditory circuits after hearing loss. We are now elucidating properties, mechanisms, and function of this AIS plasticity. The findings will reinforce our knowledge on how neural circuit function is achieved and maintained in an experience dependent manner.