Reduced synaptic activity precedes synaptic stripping in vagal motoneurons after axotomy

Abstract

Activated microglia, which spread on the motor neurons following nerve injury, engage in the displacement of detached afferent synaptic boutons from the surface of regenerating motor neurons. This phenomenon is known as "synaptic stripping." The present study attempted to examine whether changes in the synaptic inputs after motor nerve injury correlated with the microglial attachment to the dorsal motor neurons of the vagus (DMV). DMV neurons in Wistar rats could survive after nerve injury, whereas most of injured DMV neurons in the C57BL/6 mice died. At 2 days after nerve injury, a significant decrease was observed in the frequencies of both spontaneous and miniature EPSCs and IPSCs recorded from DMV neurons in the slice preparation but not from the mechanically dissociated neurons in the Wistar rats. At this stage, no direct apposition of microglia on the injured neurons was observed. High-K(+) stimulation restored their frequencies to control levels. Furthermore, PPADS and DPCPX, antagonists of P2 and adenosine receptors, respectively, also stimulated the recovery of their frequencies. In contrast, no significant change was detected in the spontaneous EPSCs frequency recorded from the severely injured DMV neurons in the slice preparation of the C57BL/6 mice. These observations strongly suggest that presynaptic inhibition through glia-derived ATP and adenosine, thus precedes synaptic stripping in regenerating DMV neurons following nerve injury.