Erzurumlu R S, Ebner F F
Center for Neural Science, Brown University, Providence, Rhode Island 02912.
J Comp Neurol. 1988 Jun 22;272(4):536-44. doi: 10.1002/cne.902720407.
Embryonic neocortical tissue survives and differentiates when grafted to injured adult neocortex. While these transplants are readily innervated by the host cholinergic fibers, specific thalamic fibers fail to innervate them. The present study was designed to test whether changing the activity levels of the thalamic ventrobasal projection neurons would promote sprouting of their axons into the embryonic cortical implants placed in the barrel field cortex. To achieve this the main input to these thalamic neurons was eliminated two synapses away, by blocking the peripheral sensory input to the barrel field cortex. Adult hosts underwent unilateral transection of the infraorbital nerve and two days later the contralateral barrel field cortex was lesioned enough to insert an embryonic neocortical graft. Following a one month post-transplantation period we examined the amount of specific thalamic axon ingrowth into the transplants by injecting the ventrobasal nucleus with horseradish peroxidase. The control cases without prior nerve damage confirmed previous observations that ventrobasal nucleus neurons fail to innervate the implanted neocortex. Transection of the infraorbital nerve prior to transplantation resulted in an unprecedented ingrowth of specific thalamic axons into the transplants. There was no significant difference in the amount of thalamic fiber ingrowth into the transplants when the peripheral nerve was (transection) or was not (cautery) allowed to regenerate. However, transection of the infraorbital nerve permits the nerve to regenerate and at least partially reconnect the sensory periphery, thus leading to the possibility of functional integration of the neocortical transplants into the host trigeminal system. The morphology and distribution of host acetylcholinesterase-positive fibers that grow into the transplants under both experimental and control conditions were distinctly different from those of thalamic axons. These results provide the first demonstration of peripheral sensory nerve induction of regenerative propensity in specific thalamocortical projection neurons. The thalamic fiber ingrowth should lead to enhanced functional innervation of the neocortical implants and better incorporation of the graft into the adult host brain circuitry.
胚胎新皮质组织移植到受损的成年新皮质时能够存活并分化。虽然这些移植组织很容易被宿主胆碱能纤维支配，但特定的丘脑纤维却无法支配它们。本研究旨在测试改变丘脑腹基底投射神经元的活动水平是否会促进其轴突发芽，长入置于桶状皮质的胚胎皮质植入物中。为了实现这一点，通过阻断桶状皮质的外周感觉输入，在两个突触之外消除了这些丘脑神经元的主要输入。成年宿主接受眶下神经单侧横断，两天后对侧桶状皮质受损，足以植入胚胎新皮质移植物。移植一个月后，我们通过向腹基底核注射辣根过氧化物酶，检查特定丘脑轴突长入移植组织的数量。没有先前神经损伤的对照病例证实了之前的观察结果，即腹基底核神经元无法支配植入的新皮质。移植前眶下神经横断导致特定丘脑轴突前所未有的长入移植组织。当外周神经（横断）或未（烧灼）允许再生时，丘脑纤维长入移植组织的数量没有显著差异。然而，眶下神经横断允许神经再生并至少部分重新连接感觉外周，从而导致新皮质移植组织功能整合到宿主三叉神经系统的可能性。在实验和对照条件下长入移植组织中的宿主乙酰胆碱酯酶阳性纤维的形态和分布与丘脑轴突明显不同。这些结果首次证明了外周感觉神经对特定丘脑皮质投射神经元再生倾向的诱导作用。丘脑纤维长入应会增强新皮质植入物的功能性神经支配，并使移植物更好地融入成年宿主脑回路。
