The Mechanism of of hyperexcitability in ALS using ALS model mice
高田 美絵子
Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, 2024/04 -2027/03, Grant-in-Aid for Scientific Research (C), Doshisha University
行動変容を導く皮質ー皮質下相互作用
田中 康裕; 高田 美絵子; 倉本 恵梨子
意思決定に関わる神経回路として大脳皮質-大脳基底核-視床ループがある。この回路について解剖学から得られた知見として、並列する複数のループからなることが挙げられる。つまり、大脳基底核の入力部位である線条体には入力元となる皮質を違えた分画があり、大脳基底核の出力部位である黒質から視床に至るまで、独立した結合関係を保ちつつループ構造を作っているという知見である。本研究は意思決定学習過程における大脳皮質-大脳基底核-視床並列ループの脳ダイナミクス(脳情報動態)変化及びその働きを解明することを目的としている。ラットを用いた視覚刺激判別による意思決定課題の開発を行った。また、訓練過程で電気生理記録を行うため、ニューロピクセル電極を用いた慢性記録のための技術開発を行った。複数カメラの設置や同期などを行い、高次元行動変容データの取得を行った。また、2光子顕微鏡下での課題装置の構築を行った。脳情報動態計測を促進するために、A01井上との共同研究として井上らが独自に開発したウイルスの供与を受け、これを用いた解析を行っている。
ニューロピクセル電極を用いて、帯状皮質-背内側線条体、運動皮質-背外側線条体などの2つのループで同時記録を行い解析している。また、電極記録位置の3次元同定を簡便化する開発を行った。具体的には簡易型のライトシート顕微鏡を作成し、固定脳の透明化法と合わせることで、蛍光染料を塗布した電極位置を脳切片を作ることなく観察することが可能となった。, 日本学術振興会, 科学研究費助成事業, 2022/06 -2027/03, 学術変革領域研究(A), 玉川大学
Neural circuits involved in switching escape/attack behavior
Takada (Morishima) Mieko
To clarify the information processing system involved in switching between escape/attack behaviors, we focused on the parabrachial nucleus, which projects to the ventral medial nucleus of the hypothalamus. Life-sustaining information is sent from the parabrachial nucleus to c via axons under stressful or threatening environments. On the other hand, the parabrachial nucleus also projects axons to the central nucleus of the amygdala, which is known to send information related to emotions such as aversion. In this study, we investigated excitatory neurons in the lateral amygdala, which is known to provide excitatory input to the central nucleus of the amygdala. We found that there are two types of excitatory neurons with different responses in aversive learning, and that they have different information processing systems., Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, 2021/04 -2024/03, Grant-in-Aid for Scientific Research (C)
Experience-dependent mechanisms for morphological and functional specification of cortical interneurons
Sugiyama Sayaka
The young brain experiences a unique window 'critical period' when neuronal circuitry is intensively remodeled based on individual experience. Since impairment of the critical periods is observed in developmental disorders and mental illnesses, it is priority issue to clarify the mechanisms. Here, we showed that unbalanced development in cortical interneuron subtypes induced the uneven development (with impairment of critical period and improvement of visual discrimination) as in autism spectrum disorders. We further identified experience-dependent molecular mechanisms to specify the interneuron subtypes and demonstrated that distinct dendritic morphology and function depending on subtypes tightly linked to sensory perception in behaving animals. Therefore, individual experience increased the heterogeneity of intracortical circuits to enable functional individuality., Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, 2019/04 -2022/03, Grant-in-Aid for Scientific Research (B), Niigata University
Cortical local circuits for multi-area interconnectivity and parallel processing
KAWAGUCHI Yasuo
Since the frontal cortex, unlike the sensory cortex, makes connecting loops with the basal ganglia and influences other cortical regions by top-down corticocortical projections, we thought it had a unique circuit structure and investigated the connectivity rules between neuron subtypes and the functions of individual subtypes. For this analysis, we developed techniques for correlating two-photon, light, and electron microscope images. As a result, we have established an automated tape collecting ultramicrotome/scanning electron microscope system for cortical circuit analysis. In the frontal cortex, we found that differentially connected subnetworks between bilaterally and unilaterally projecting corticocortical pyramidal cells, diversity of bilaterally projecting pyramidal cells, motor learning control by local oscillations dependent on a specific subtype of pyramidal cells, and synaptic input type-dependent connection reconstruction during motor learning., Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, 2017/06 -2022/03, Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
Development of a Nonlinear Timeseries Analysis for Functional Neural Connectivity Estimation
Hidaka Shohei
Cortex plays important roles in higher order functions as well as perception, motor control, and emotion. Previous studies have reported microscopic findings on individual structure of neural circuits and macroscopic findings on activities in a particular brain area correlated with a class of tasks. It is, however, largely unknown on the meso-scopic scale or the intermediate level connecting both. This study has developed a new information technique for estimating the functional neural connectivity from the timeseries data obtained by the Ca imaging method. We validated the developed technique with both empirical and simulated datasets, and showed that it could detect a set of sub-groups of neurons with dense functional connectivity., Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, 2015/07 -2019/03, Grant-in-Aid for Scientific Research (B), Japan Advanced Institute of Science and Technology
Excitatory-Inhibitory reccurent networks in layer5 frontal cortex
TAKADA Mieko
Neocortical pyramidal cells send axons to diverse extracortical targets, but also issue the intracortical collaterals innervating other pyramidal cells as well as GABAergic cells. Recently it has been proposed that most of GABAergic interneurons make synapses on nearby pyramidal cells in a non-selective manner. On the other hand, synaptic connections between pyramidal cells are selectively formed according to extracortical projection patterns. Therefore, we analyzed synaptic connections between GABAergic interneurons and pyramidal cells specified projection targets. First, we investigated the connections with FS (fast spiking) cells.The connection probability from pyramidal cells to FS was similar. The short term plasticity of EPSCs was depressive in most connections from CCS to FS cell, but facilitatory in connections from CPn to FS cells. These results suggest that the intracortical inhibitory system is organized according to diverse pyramidal projection subtypes., Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, 2012/04 -2014/03, Grant-in-Aid for Young Scientists (B), National Institute for Physiological Sciences
Integration of cortical micro and macro circuits
KAWAGUCHI Yasuo; TAKADA Mieko; KUBOTA Yoshiyuki
Using neocortex, especially frontal cortex, and basal ganglia, animals select the most appropriate actions according the past action and its result. To understand this brain process, we should know the neuron composition of the frontal cortex and their synaptic interactions. This research has clarified the functional organization and synaptic connection rules of output cells projecting to the basal ganglia and other subcortical structures. These findings indicate that the neocortical local circuit consists of connection subnetworks organized according to diverse extracortical projections., Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, 2009 -2012, Grant-in-Aid for Scientific Research (A), National Institute for Physiological Sciences
The mechanism of excitatory neuron and inhibitory neuron in local circuit of frontal cortex
TAKADA Mieko
In cerebral cortex, cerebral circuits are composed of excitatory neurons and inhibitory neurons. To reveal the mechanism of the cerebral circuits, it is important to study how the excitatory neuron and inhibitory neurons communicate each other. I investigated the connection pattern of two groups of pyramidal cells and specific inhibitory neurons. I found that the specific inhibitory neurons selectively innervate the two groups of pyramidal cells., Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, 2008 -2009, Grant-in-Aid for Young Scientists (B), National Institute for Physiological Sciences
Local circuit differentiation of frontal cortex dependent on subcortical projection
KAWAGUCHI Yasuo; TAKADA Mieko
大脳皮質錐体細胞の機能的分化を生理学・薬理学的に検索した。錐体細胞は皮質外投射先によって発火特性やアセチルコリン作用が異なることを見つけた。新皮質の2/3層から5層錐体細胞への興奮性結合は5層錐体細胞サブタイプによって、シナプス結合の確率・結合細胞の空間分布・発散結合の選択性が異なることが分かった。, Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, 2007 -2008, Grant-in-Aid for Scientific Research (B), National Institute for Physiological Sciences
大脳皮質-線条体間の神経回路の解析
高田 美絵子
ラット前頭皮質5層,線条体投射錐体細胞には二種類あることが知られている。一つは同側線条体へ軸索側枝を伸ばし更に脳幹へ投射する細胞(crossed corticopontine cell ; CPn細胞)、もう一つは両側線条体へ投射するが脳幹へは軸索を伸ばさない細胞(crossedcorticostriatal cell ; CCS細胞)である。この二種類の錐体細胞の形態的特徴・皮質内結合を調べることは、V層における投射の異なる細胞間の結合選択性を明らかにするだけでなく、大脳基底核への皮質入力の役割を理解する上でも重要である。本研究では、上記の二種類のニューロンを橋と対側線条体に二種類の異なる逆行性色素を注入することで同定し、同時にホールセル・パッチクランプ記録を行うことによってシナプス特性及び神経結合を調べた。電気生理実験終了後、記録細胞を細胞内染色しニューロルシーダで三次元再構築して形態学的解析を行い、以下のことがわかった。
1.尖端樹状突起形態がタイプ間で異なり、CPn細胞の方がシャフト起始部の直径が大きく、I層におけるタフト構造が発達していた。
2.タイプ間のシナプス結合には方向性があり、CCS細胞間及び、CCSからCPn細胞への結合は約10%で見られたのに対して、CPnからCCS細胞への結合はほとんどみられなかった。
4.CCS細胞からのシナプス電流の時間経過は、シナプス後錐体細胞のタイプによらなかった。軸索ブトンのコンタクト数は、CCS細胞へのシナプス電流の大きさとよく相関し、変動係数・欠落率と逆相関していた。
5.CCS細胞間では主に基底樹状突起にコンタクトがみられ、CCS-CPn細胞間では尖端樹状突起にもみられた。コンタクト数はCPn細胞への方が多くみられた。, 日本学術振興会, 科学研究費助成事業, 2004 -2005, 特別研究員奨励費, 総合研究大学院大学