Functional Diversity of Neurotrophin Actions on the Oculomotor System

Abstract

Neurotrophins play a principal role in neuronal survival and differentiation during development, but also in the maintenance of appropriate adult neuronal circuits and phenotypes. In the oculomotor system, we have demonstrated that neurotrophins are key regulators of developing and adult neuronal properties, but with peculiarities depending on each neurotrophin. For instance, the administration of NGF (nerve growth factor), BDNF (brain-derived neurotrophic factor) or NT-3 (neurotrophin-3) protects neonatal extraocular motoneurons from cell death after axotomy, but only NGF and BDNF prevent the downregulation in ChAT (choline acetyltransferase). In the adult, in vivo recordings of axotomized extraocular motoneurons have demonstrated that the delivery of NGF, BDNF or NT-3 recovers different components of the firing discharge activity of these cells, with some particularities in the case of NGF. All neurotrophins have also synaptotrophic activity, although to different degrees. Accordingly, neurotrophins can restore the axotomy-induced alterations acting selectively on different properties of the motoneuron. In this review, we summarize these evidences and discuss them in the context of other motor systems.

Synaptic Plasticity on Motoneurons After Axotomy: A Necessary Change in Paradigm

“…These findings were replicated on postganglionic sympathetic neurons whose axons were treated with colchicine (Purves, 1976). Target-dependence of motoneuron properties became a very active area of research with many comprehensive reviews on the topic (Mendell, 1984;Titmus and Faber, 1990;de la Cruz et al, 1996;Terenghi, 1999;Navarro et al, 2007;Benítez-Temiño et al, 2016). Here, we will focus on how these studies inform about differences in the removal and recovery of different synapses.…”

“…A comprehensive direct comparison of the effects of different neurotrophins on preservation and recovery of specific synaptic inputs was carried out by the group of Dr. Angel Pastor (University of Seville) using as a model the axotomy of abducens motoneurons. This work draws on extensive knowledge about the synaptic inputs controlling tonic and phasic firing of abducens motoneurons in relation to eye position, eye velocity, and vestibular stimulation (reviewed in Benítez-Temiño et al, 2016). NT3 and BDNF were applied to the cut nerve at the time of injury (to test preservation) or after a 2-week delay allowing synaptic stripping (to test recovery).…”

Extraocular Muscle Repair and Regeneration

“…This myogenic precursor cell-rich environment may be supported by the maintained expression in adult EOMs of a number of neurotrophic factors that are normally down-regulated in skeletal muscles [75], including insulin-like growth factor-1 and -2 [76, 77], brain derived neurotrophic factor [78, 79], glial derived neurotrophic factor [80, 81], and neurotrophin-3 [78]. All of these neurotrophic factors are critical for maintenance of the ocular motor neurons in development [82, 83].…”

Myosin heavy chains in extraocular muscle fibres: Distribution, regulation and function

“…In recent years, neurotrophins have emerged as playing important roles not only during neuronal development but also in adult life, when they act as mediators of synaptic and morphological plasticity 186,187 . The integrity and synaptic connectivity of ocular motoneurons are sustained by different retrogradely transported muscle‐derived neurotrophins, as in the case of spinal and other craniofacial motoneurons 188 .…”