Fast retrograde effects on neuronal death and dendritic organization in development: The role of calcium influx

Retrograde signals from axon terminal to cell body are known to regulate ne uronal survival and differentiation during development. They are generally attributed to the uptake and transport of trophic factors, but there is rec ent evidence in the isthmo-optic nucleus For a remarkably fast-acting retro grade signal from the contralateral retina that is not mediated by the conv entional trophic route. The isthmo-optic nucleus undergoes 55% neuron death between embryonic days 12 and 17, and becomes laminated at embryonic day 1 4 owing to dendritic re-organization. Blockade of retinal electrical activi ty just before day 14 reduces neuronal death and lamination in the isthmo-o ptic nucleus within as little as 6 h. We here investigate how action potentials initiate the fast-acting retrogra de signal, and we provide evidence that the first step is calcium entry int o the isthmo-optic axon terminals. Neuronal death and lamination are rapidl y reduced in the isthmo-optic nucleus by intraocularly injected omega-conot oxin, a blocker of N-type calcium channels known to be located mainly on ax on terminal. Similar effects occurred with two other calcium channel blocke rs (cadmium and a-bungarotoxin) believed to act on both the isthmo-optic te rminals and their target cells, but not with nifedipine, a blocker of L-typ e (mainly somatic) channels, supporting a presynaptic initiation of the fas t signal. Nevertheless postsynaptic events may also be involved because pha rmacological destruction of the amacrine targets cells of the isthmo-optic nucleus reduced its cell death and lamination 9-12 h later. (C) 1998 IBRO. Published by Elsevier Science Ltd.