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The aim of the present work was to characterize the axotomy-induced changes in the discharge properties of central nervous system neurons recorded in the alert behaving animal. The abducens internuclear neurons of the adult cat were the chosen model. The axons of these neurons course through the contralateral medial longitudinal fascicle and contact the medial rectus motoneurons of the oculomotor nucleus. Axotomy was carried out by the unilateral transection of this fascicle (right side) and produced immediate oculomotor deficits, mainly the incapacity of the right eye to adduct across the midline. Extracellular single-unit recording of abducens neurons was carried out simultaneously with eye movements. The main alteration observed in the firing of these axotomized neurons was the overall decrease in firing rate. During eye fixations, the tonic signal was reduced, and, on occasion, a progressive decay in firing rate was observed. On-directed saccades were not accompanied by the high-frequency spike burst typical of controls; instead, there was a moderate increase in firing. Similarly, during the vestibular nystagmus, neurons hardly modulated during both the slow and the fast phases. Linear regression analysis between firing rate and eye movement parameters showed a significant reduction in eye position and velocity sensitivities with respect to controls, during both spontaneous and vestibularly induced eye movements. These firing alterations were observed during the 3 month period of study after lesion, with no sign of recovery. Conversely, abducens motoneurons showed no significant alteration in their firing pattern. Therefore, axotomy produced long-lasting changes in the discharge characteristics of abducens internuclear neurons that presumably reflected the loss of afferent oculomotor signals. These alterations might be due to the absence of trophic influences derived from the target. J. Comp. Neurol. 427:391‐ 404, 2000. © 2000 Wiley-Liss, Inc.

In this review we have attempted to summarize present knowledge concerning the regulatory role of target cells on the expression and maintenance of the neuronal phenotype during adulthood. It is well known that in early developmental stages the survival of neurons is maintained by specific neurotrophic factors derived from their target tissues. Neuronal survival is not the only phenotype that is regulated by target-derived neurotrophic factors since the expression of electrophysiological and cytochemical properties of neurons is also affected. However, a good deal of evidence indicates that the survival of neurons becomes less dependent on their targets in the adult stage. The question is to what extent are target cells still required for the maintenance of the pre-existing or programmed state of the neuron; i.e., what is the functional significance of target-derived factors during maturity? Studies addressing this question comprise a variety of neuronal systems and technical approaches and they indicate that trophic interactions, although less apparent, persist in maturity and are most easily revealed by experimental manipulation. In this respect, research has been directed to analyzing the consequences of disconnecting a group of neurons from their target-by either axotomy or selective target removal using different neurotoxins-and followed (or not) by the implant of a novel target, usually a piece of embryonic tissue. Numerous alterations have been described as taking place in neurons following axotomy, affecting their morphology, physiology and metabolism. All these neuronal properties return to normal values when regeneration is successful and reinnervation of the target is achieved. Nevertheless, most of the changes persist if reinnervation is prevented by any procedure. Although axotomy may represent, besides target disconnection, a cellular lesion, alternative approaches (e.g., blockade of either the axoplasmic transport or the conduction of action potentials) have been used yielding similar results. Moreover, in the adult mammalian central nervous system, neurotoxins have been used to eliminate a particular target selectively and to study the consequences on the intact but target-deprived presynaptic neurons. Target depletion performed by excitotoxic lesions is not followed by retrograde cell death, but targetless neurons exhibit several modifications such as reduction in soma size and in the staining intensity for neurotransmitter-synthesizing enzymes. Recently, the oculomotor system has been used as an experimental model for evaluating the functional effects of target removal on the premotor abducens internuclear neurons whose motoneuronal target is destroyed following the injection of toxic ricin into the extraocular medial rectus muscle. The functional characteristics of these abducens neurons recorded under alert conditions simultaneously with eye movements show noticeable changes after target loss, such as a general reduction in firing frequency and a loss of the discharge signals related to eye position and velocity. Nevertheless, the firing pattern of these targetless abducens internuclear neurons recovers in parallel with the establishment of synaptic contacts on a presumptive new target: the small oculomotor internuclear neurons located in proximity to the disappeared target motoneurons. The possibility that a new target may restore neuronal properties towards a normal state has been observed in other systems after axotomy and is also evident from experiments of transplantation of immature neurons into the lesioned central nervous system of adult mammals. It can be concluded that although target-derived factors may not control neuronal survival in the adult nervous system, they are required for the maintenance of the functional state of neurons, regulating numerous aspects of neuronal structure, chemistry and electro-physiology.(ABSTRUCT TRUNCATED)