移植脳細胞，宿主脳細胞間のシナプス形成メカニズム—電気生理学的研究

Synaptogenesis between the host and the grafted neurons in the central nervous system. An electrophysiological study.

I．はじめに

　脳組織の移植に関する研究は19世紀末にすでに始められているが，本格的な研究が始められたのは1970年代に入ってからである。その後，この分野での研究は各国でさかんに進められ，パーキンソン病や，アルツハイマー病の治療に応用されようとしている^3,6,10,33）。脳細胞という一度脱落すると再生，補充されない特殊な細胞を扱う脳神経外科の立場からみても，失われた細胞を補充して機能の回復をはかるというまったく新しい治療手段は大変魅力的なものであるが，脳組織移植に使用できる脳は胎児脳に限られるため，倫理的問題がつきまとい，現時点での臨床応用は困難である。そこで自己の副腎髄質の移植が試みられている^1,24）。しかし，脳移植は中枢神経細胞の分化，生長，再生，標的組織の認識，シナプス形成などの基礎的問題の研究手段としては非常に有力である。

　移植された脳細胞は単に盲目的に周囲に神経線維を伸ばすのではなく，胎仔脳組織をその標的組織の近くに移植すると，移植された脳細胞から標的組織へ向かって神経線維が伸びていくことは，すでに多くの研究グループによって証明されている^{2,3,5,16,21,26,28,30,38,39,41,47）}。

It is well known that the grafted neurons extend fibers into the host brain, when they were placed near the target tissue. But the specificity of the synaptogenesis to the target cells and the electrical property of the synapses formed between these two structures had not yet been studied. These problems were studied electrophysiologically with the rat visual system of which synaptic connection pattern is well known.

The lateral geniculate nucleus (LGN) of a fetal Wistar rat was implanted into the visual cortex (VC) of a host Wistar rat. After 2 to 6 months, host rats were sacrificed and the occipital cortex containing the LGN graft were excised. Brain slice preparations were made from the occipital cortex and then placed in a experimental chamber. The synaptic connections between the host occipital cortex and the grafted LGN were studied electro-physiologically using in vitro slice preparations. Current source-density analysis of the field poten-tials recorded in the host occipital cortex, which were evoked by stimulating the LGN graft, sug-gested that the grafted LGN cells made dense excitatory monosynaptic connections in the layerIV of area 17 of the host occipital cortex which is the proper target tissue of the dorsal LGN neurons. Then intracellular recordings were made in the host VC cells to clarify the electrical pro-perty of the synapses that were made between the LGN graft cells and the host VC cells. When the LGN graft was stimulated, excitatory post synaptic potentials (EPSPs) or EPSPs followed by inhibi-tory post synaptic potentials (IPSPs) were recorded in the host VC cells. Analysis of the latencies of the EPSPs revealed that the grafted LGN cells made excitatory monosynaptic connections to the VC cells in layer IV-III of area 17 and made excitatory disynaptic connections to the VC cells in layer II of area 17. Stimulating the host visual cortex, intracellular recordings were also made in the grafted LGN cells. In about 50% of the rec-orded LGN cells, antidromic spikes were demon-strated. In about 60% of the recorded LGN cells, EPSPs or EPSPs followed by IPSPs were recorded. In some LGN cells, both antidromic and ortho-dromic responses were recorded. After recording, HRP was injected electrophoretically into the grafted LGN cells. HRP intracellular staining demonstrated that the LGN cells in which anti-dromic spikes were recorded were multipolar type neurons, which coincides with the previous mor-phological study of the relay cells in the dorsal LGN.