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

Abstract

ABSTRACT Axons deprived of their nucleus degenerate within a few days in mammals but survive for several months in crustaceans. However, it is not known whether central synapses from sensory axons may preserve their molecular machinery in the absence of spiking activity. To assess this, we used peripheral axotomy, which removes their nuclei combined with electrophysiology techniques and electron microscopy imaging. We report the following. (1) Electron microscopy analysis confirms previous observations that glial cell nuclei present in the sensory nerve proliferate and migrate to axon tubes, where they form close contacts with surviving axons. (2) After peripheral axotomy performed in vivo on the coxo-basipodite chordotonal organ (CBCO), the sensory nerve does not convey any sensory message, but antidromic volleys are observed. (3) Central synaptic transmission from the CBCO to motoneurons (MNs) progressively declines over 200 days (90% of monosynaptic excitatory transmission is lost after 3 weeks, whereas 60% of disynaptic inhibitory transmission persists up to 6 months). After 200 days, no transmission is observed. (4) However, this total loss is apparent only because repetitive electrical stimulation of the sensory nerve in vitro progressively restores first inhibitory post-synaptic potentials and then excitatory post-synaptic potentials. (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 show that antidromic activity in the CBCO nerve could play a role in the maintenance of synaptic function of inhibitory pathways to MNs, but not monosynaptic excitatory transmission to MNs. Our study confirms the deep changes in glial nuclei observed in axons deprived of their nucleus. We further show that the machinery for spike conduction and synaptic release persists for several months, even if there is no longer any activity. Indeed, we were able to restore, with electrical activity, spike conduction and synaptic function after long silent periods (>6 months).