Activity-dependent decline and recovery of synaptic transmission in central parts of surviving primary afferents after their peripheral cut.

Abstract

Whereas axons deprived of their nucleus degenerate within a few days in Mammals, they survive for several months in Crustacean. However, it is not known if central synapses from sensory axons may preserve their molecular machinery in the absence of spiking activity, after peripheral axotomy, which suppress their nucleus. Using electrophysiology techniques and electron microscopy imaging we report that 1) Electron microscopy analysis confirms previous observations that glial cell nucleus present in sensory nerve, proliferate an migrate to axon tubes, in which they form close contact with surviving axons; 2) after peripheral axotomy performed in vivo on Coxo-Basipodite chordotonal organ (CBCO) sensory nerve does not convey any sensory message, but antidromic volleys are observed; 3) Central synaptic transmission to motoneurons (MNs) progressively declines over #200 days (90% of monosynaptic excitatory transmission is lost after 3 weeks, whereas 60% of polysynaptic inhibitory transmission persist up to 6 months). After #200 days no transmission is observed anymore; 4) However, this total loss is only apparent, because repetitive electrical stimulation of the sensory nerve in vitro progressively restores first inhibitory post-synaptic potentials (IPSPs) then excitatory post-synaptic potentials (EPSPs); 5) The loss of synaptic transmission can be prevented by in vivo chronic sensory nerve stimulation; 6) Using simulations based on the geometric arrangements of synapses of the monosynaptic excitatory transmission and disynaptic inhibitory pathways, we have shown that antidromic activity in CBCO nerve could play a role in maintenance of synaptic function of inhibitory pathways to MNs, but not on monosynaptic excitatory transmission to MNs. Taken together, our study confirms the key role of glial nucleus in axon survival, that machinery for spike conduction and synaptic release even if no activity is present for several months. After long silence periods (>6 months) spike conduction and synaptic function can still be restored by electrical activity.