Early pre- and postsynaptic decrease in glutamatergic and cholinergic signaling after spinalization is not modified...

Area of Science:

• Neuroscience
• Motor Neuron Physiology
• Spinal Cord Injury Research

Background:

• Chronic spinalization (SCT) in rats leads to reduced peripheral inputs (Ia proprioceptive and cholinergic) in ankle extensor motoneurons (MNs).
• Ankle flexor MNs show less vulnerability to SCT, highlighting a need for targeted interventions.
• Previous studies suggest low-threshold proprioceptive stimulation can enhance inputs to extensor MNs in intact spinal cords.

Purpose of the Study:

• To investigate the effectiveness of selective proprioceptive stimulation in restoring glutamatergic Ia and cholinergic inputs to lateral gastrocnemius (LG) MNs after chronic spinalization (SCT).
• To examine the impact of this stimulation on postsynaptic receptor expression (NMDAR, M2 muscarinic, AMPAR) in LG MNs post-SCT.

Main Methods:

• Rats underwent bilateral tibial nerve and soleus muscle implantation prior to spinalization.
• Fluorescence tracers were injected to identify LG and tibialis anterior (TA) MNs.
• Tibial nerve stimulation, guided by soleus H-reflex, commenced on post-SCT day 3 for 7 days.

Main Results:

• SCT decreased the number and volume of glutamatergic Ia and cholinergic C-boutons on LG MNs.
• The applied stimulation did not counteract these decreases in presynaptic inputs.
• SCT caused significant reductions in NMDAR NR1 and M2 muscarinic receptor transcripts, which were not improved by stimulation; AMPAR GluR2 subunit transcripts tended to decrease further.

Conclusions:

• Early proprioceptive stimulation after SCT does not induce compensatory transcriptional responses in LG MNs.
• LG MNs, despite receiving proprioceptive input, fail to translate these cues into molecular adaptations in the early post-injury period.
• Selective stimulation approaches may require different timing or modalities to effectively restore MN function after spinal cord injury.