“Development of basic technology for visualization and observation of brain neural circuitry”

Elucidating neuronal circuits is one of the fundamental issues for understanding how the brain works and implements higher-order functions. For the analysis of three-dimensional structures of neurons, a traditional method has been so far adopted: 1) preparation of thin sections (30–40 µm), 2) immunostaining of the target structures, and 3) reconstruction of the structures with the aid of software. Since this conventional method is time-consuming and often tedious, the new method for neuron tracing and reconstruction has been eagerly anticipated. Our group focuses on integrative technology for structural analysis toward the development of efficient evaluation method for neuronal circuits, especially visualization and observation methods.

Various virus vectors have been developed, and become valuable tools for the analysis of neuronal circuits in the central nervous system. We have developed and succeeded in high-level transgene expression in central neurons by lentivirus vectors with Tet-Off system (Hioki et al., 2007, 2009). We apply the Tet-Off/On system to adeno-associated virus (AAV) vectors, to establish more convenient and promising tools for visualization and manipulation of brain neural circuitry.

Our group is also engaged in the development of tissue-clearing technology, and developed ScaleS, a sorbitol-based optical clearing method that provides stable tissue preservation (Hama et al., 2015). This technique enables us to perform deep and high-resolution biological imaging with thick section or whole brain samples. We continue the development of both basic and practical technology, and prompt the morphological analysis in this area, “Adaptive Circuit Shift. ”

 

 
Recent Publications
1. Hama H, Hioki H, Namiki K, Hoshida T, Kurokawa H, Ishidate F, Kaneko T, Akagi T, Saito T, Saido T, *Miyawaki A (2015) ScaleS: an optical clearing palette for biological imaging. Nat Neurosci 18:1518-1529.
2. Nakamura H, *Hioki H, Furuta T, Kaneko T (2015) Different cortical projections from three subdivisions of the rat lateral posterior thalamic nucleus: a single-neuron tracing study with viral vectors. Eur J Neurosci 41:1294-1310.
3. Kataoka N, Hioki H, Kaneko T, *Nakamura K (2014) Psychological stress activates a dorsomedial hypothalamus-medullary raphe circuit driving brown adipose tissue thermogenesis and hyperthermia. Cell Metab 20:346-358.
4. Hioki H, Okamoto S, Konno M, Kameda H, Sohn J, Kuramoto E, Fujiyama F, *Kaneko T (2013) Cell type-specific inhibitory inputs to dendritic and somatic compartments of parvalbumin-expressing neocortical interneuron. J Neurosci 33:544-555.

Posted:2016/03/10