Brain Research, 340 (1985) 115-125 1 15 Elsevier BRE 10888 Functional Activity of Rat Brainstem Neurons Regenerating Axons Along Peripheral Nerve Grafts MICHAEL MUNZ, MICHAEL RASMINSKY, ALBERT J. AGUAYO, MANUEL VIDAL-SANZ and MARSHALL G. DEVOR* Neurosciences Unit, Montreal General Hospital and Department of Neurology and Neurosurgery, McGill University, Montreal, Que. H3G 1A4 (Canada) (Accepted October 30th, 1984) Key words: central nervous system regeneration -- synapse -- plasticity -- somatosensory system -- gracile nucleus cuneate nucleus -- trigeminal nucleus -- receptive fields To investigate activation and discharge patterns of central nervous system neurons that regenerate lengthy axons along peripheral nerve grafts we inserted a 4 cm long autologous segment of sciatic nerve into the dorsolateral medulla oblongata of adult rats. Two to 6 months after grafting, the distribution of the cells of origin of the regenerating axons in many nuclei of the brainstem was documented by retrograde horseradish peroxidase labelling from the cut end of the grafts. Functional properties of neurons regenerating axons into the grafts were studied by recording from single regenerated fibers teased from the grafts. Conduction velocities of graft fibers ranged from < 1 m/s to 25 m/s (30 °C). Spontaneous centrifugal impulse traffic in the grafts included units firing in bursts synchronously w~th the respiratory cycle. Activity in other units was either elicited or mhl0~ted by natural or electrical stimulation of the periphery. Most units recorded in the grafts were neither spontaneously active nor responsive to stimulation of primary affercnts. We conclude that: (1) there are central nervous system neurons projecting into the grafts that respond to both excitatory and inhibitory transsynap- tic influences; (2) at least some of the spontaneous and induced activity recorded from axons in the grafts resembles that known for normal nerve cells in the regions of the brainstem from which axonal growth arises; and (3) it is possible that many central neurons re- generating axons into peripheral nerve grafts have significantly reduced or altered synaptic inputs. INTRODUCTION Anatomic studies have recently demonstrated that neurons in the adult mammalian central nervous sys- tem (CNS) are capable of extensive axonal elonga- tion after injury 2,4&9,3t,32. In these experiments it was shown that axonal regrowth, usually limited in the CNS, is markedly enhanced when central neurons are made to interact with transplanted segments of peripheral nerve. This potential for axonal regenera- tion from CNS neurons was demonstrated by insert- ing peripheral nerve grafts into lesions in the CNS of rats to provide central axons with a neuron-free con- duit composed of Schwann cells and other cellular and non-cellular components of the peripheral ner- vous system (PNS). With neuroanatomic tracer tech- niques we established that nerve cells in the spinal cord, brainstem, thalamus, basal ganglia and cere- bral cortex can regrow axons for distances equivalent to those of the long tracts and association fibers that normally join widely separated regions of the neurax- is 2,4,5,9. Many if not all of these axons arise from dam- aged axons or collaterals ~0,13.35. These anatomic investigations established the cen- tral origin of many of the axons extending into the PNS grafts, but gave no information as to whether or not these nerve cells retained such functional prop- erties as impulse propagation along the regenerated axon, responsiveness to afferent inputs or character- istic patterns of spontaneous and evoked activity. These functional attributes cannot be taken for granted both because of the unusual conditions of the regeneration and because intrinsic excitability and afferent connectivity can be significantly altered in * Permanent address: Life Sciences Institute, Hebrew University, Jerusalem, Israel 91904. Correspondence: M. Rasminsky, Division of Neurology, Montreal General Hospital, 1650 Cedar Ave., Montreal, Que., H3G I A4, Canada. 0006-8993/85/$03.30 © 1985 Elsevier Science Publishers B.V. (Biomedical Division)