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ラットの視床髄板内核群内に存在するoval paracentral nucleusから大脳皮質への投射とその特異性の解明

水野, 友香 大阪大学 DOI:10.18910/87975

2022.03.24

概要

【背景と目的】
 閉口筋筋紡錘感覚は三叉神経上核経由で、視床の後内側腹側核尾腹内側縁(VPMcvm)と髄板内核の中心傍核(PC)の尾側部内に存在するoval paracentral nucleus(OPC)に投射している(Yoshida et al. 2017;Sato et al. 2020)。VPMcvmは、二次体性感覚野(S2)の最吻側部に接してその吻腹側に位置する顆粒性島皮質背側部(dGIrvs2)のみに投射する。よって、閉口筋筋紡錘感覚の情動への強い関与が示唆されている(Sato et al. 2017)。そこで、本研究では、0PCの大脳皮質への投射部位を明らかにし、他の髄板内核や感覚視床からの投射と比較して、その投射の特異性の解明を試みた。なお、Berendse and Groenewegen(1991)とVan der Werf et al. (2002)は、ラットの視床髄板内核から大脳皮質への投射を報告しているが、0PCとPCを区別して行っていないので、PCの尾側領域からの大脳皮質への投射も明らかにし、OPCからの投射と比較した。

【方法】Wistar系雄ラットを用い、深麻酔下で次の二つの実験を行った。
実験1 順行性トレーサーを用いた、OPCから大脳皮質への投射様態の解明
 順行性トレーサーであるbiotinylated dextranamine(BDA, 10,000MW)を封入したガラス管微小電極を露出した脳表面から刺入した。咬筋神経の電気刺激と受動的開口に対する神経応答を記録して0PCの詳細な位置を同定した後、BDAを0PC内に電気泳動にて微量注入した。

実験2 順行性トレーサーを用いた、PCの尾側部から大脳皮質への投射様態の解明
 実験1と同じ方法で同定した0PCの位置を参考にして、ガラス管微小電極をPCの尾側部に刺入し、BDAを電気泳動にて微量注入した。

実験3 逆行性トレーサーを用いた、大脳皮質に投射する視床髄板内核と感覚視床のニューロンの分布の解明
 実験1のOPCへの注入でBDA標識された軸索が多数認められた、一次体性感覚野(SI)、S2の最吻側部、S2の最吻側部を除くS2の吻側部、dGIrvs2を含む顆粒性島皮質(GI)の吻尾的中央部、dGIrvs2より尾側のGIの5ヶ所に、逆行性トレーサーであるFluorogold(FG)を封入したガラス管微小電極を、露出した脳表面から刺入し、FGを電気泳動にて微量注入した。

切片の作成
 注入の5日〜7日後に、深麻酔ドで動物を固定液で灌流固定した。全脳を摘出し、連続冠状断切片を作成した。BDAの呈色はABC法とDAB法で行なった。FGの品色は、抗FGウサギ抗体を用いた免疫組織反応の後、ABC法とDAB法で行なった。

【結果】
実験1
 OPCへのBDAの注入で、多数のBDA標識軸索終末がSI、S2、GIに認められた。S1の標識軸索終末は、S1の吻腹側1/4に認められた。これらは第IV層で高密度であり、第V層の表層(Va)と深層(Vb)でやや高密度であった。S2の標識軸索終末は、大部分がS2の吻側部に認められ、Yoshida et al.(2017)で明らかになったVPMcvm経由の閉口筋筋紡錘感覚がわずかに入力するS2の最吻側部を含んでいた。これらは第IV〜VI層にやや高密度に認められた。GITは、dGIrvs2を含むGIの吻尾的中央の背側部の第Vb層と第VI層に認められた。

実験2
 PCの尾側部へのBDAの注入で、多数のBDA標識軸索終末が、二次運動野に相当する内側無顆粒性皮質(Agm)の最吻側部の外側部と、一次運動野に相当する外側無顆粒性皮質(Ag1)の吻側部に認められた。Agmでは第VI層と第V層にやや高密度に、Ag1では第V層と第ΙΙ/Ⅲ層にやや高密度に認められた。これらの部位は、実験1で明らかにした0PCの投射部位とは驚くほど重複しておらず、S1、S2、dGIrvs2には認められなかった。

実験3
 多くの標識細胞が、S1の吻側部への注入では、core VPMと0PCに認められた。S2の最吻側部への注入では、core VPM、OPC、VPMcvmに認められた。S2の最吻側部を除くS2の吻側部への注入では、core VPM、視床後核内側部(Pom)、OPCに認められた。dGIrvs2を含むGIの吻尾的中央部への注入では、視床後腹側核小細胞部(VPPC)、VPMcvm、OPCに認められた。dGIrvs2より尾側のGIへの注入では、VPPCとOPCに認められた。これらの結果より、感覚視床と視床髄板内核の中で、上記の5つの大脳皮質領域すべてに投射するのはOPCだけであった。

【考察と結語】
 本研究により、閉口筋筋紡錘感覚を大脳皮質に伝達する新しい経路が明らかになった。このOPC経由の皮質投射は、SI、S2の最吻側部、S2の最吻側部を除くS2の吻側部、dGlrvs2を含むGIの吻尾的中央部、dGIrvs2より尾側のGIの5ヶ所のいずれにも強く投射しており、これは他の視床髄板内核や感覚視床とは大きく異なっていた。この結果は、OPC経由の閉口筋筋紡錘感覚は、口腔顔面感覚の識別および感覚の統合にも関与する可能性を示唆している。dGIrvs2はOPCとVPMcvmの両方からの投射を受ける唯一の部位であるが、VPMcvmは主にdGIrvs2の第IV層に投射したが(Sato et al. 2017)、OPCは主に第Vb層と第VI層に投射した。OPCとVPMcvm経由の閉口筋筋紡錘感覚入力は、dGIrvs2で統合されずに別々に処理される可能性を示唆している。

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