Elimination of action potentials blocks the structural development of retinogeniculate synapses

Abstract

Although the influence of electrical activity on neural development has been studied extensively^1,2, experiments have only recently focused on the role of activity in the development of the mammalian central nervous system (CNS)^3–10. Using tetrodotoxin (TTX) to abolish sodium-mediated action potentials1^1,12, studies on the visual system show that impulse activity is essential both for the normal development of neuronal size⁵ and responsivity in the lateral geniculate nucleus (LGN)^4,10, and for the eye-specific segregation of geniculo-cortical axons^3,7. There have been no anatomical studies to investigate the influence of action potentials on CNS synaptic development. We report here the first direct evidence that elimination of action potentials in the mammalian CNS blocks the growth of developing axon terminals and the formation of normal adult synaptic patterns. Our results show that when TTX is used to eliminate retinal ganglion-cell action potentials in the cat from birth to 8 weeks, the connections made by ganglion cell axons with LGN neurones, retinogeniculate synapses, remain almost identical morphologically to those in the newborn kitten.