Peripheral nerve transection induces innervation of embryonic neocortical transplants by specific thalamic fibers in adult mice.
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.
Erzurumlu
R S
RS
Center for Neural Science, Brown University, Providence, Rhode Island 02912.
Ebner
F F
FF
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000196:embryology / Q000201:enzymology / Q000637:transplantation*; D006735:Horseradish Peroxidase; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009412:Nerve Fibers / Q000201:enzymology / Q000502:physiology*; D009416:Nerve Regeneration; D009424:Nervous System Physiological Phenomena; D009915:Orbit / Q000294:innervation; D010525:Peripheral Nerves / Q000502:physiology*; D009435:Synaptic Transmission; D013787:Thalamic Nuclei / Q000201:enzymology / Q000502:physiology*
D006735:Horseradish Peroxidase; D000110:Acetylcholinesterase