Inhibitory postsynaptic potentials in lumbar motoneurons remain depolarizing after neonatal spinal cord transection...

Area of Science:

• Neuroscience
• Developmental Biology
• Physiology

Background:

• GABA and glycine are initially excitatory in the immature spinal cord, transitioning to inhibitory functions during development.
• The shift to hyperpolarizing inhibitory postsynaptic potentials (IPSPs) occurs perinatally, coinciding with brain stem projections reaching the lumbar spinal cord.
• The reversal potential of IPSPs (E(IPSP)) undergoes a critical negative shift during this developmental window.

Purpose of the Study:

• To investigate the impact of suppressing brain influences on lumbar motoneurons during the critical period of E(IPSP) maturation.
• To determine if brain stem input is essential for the developmental upregulation of KCC2 and functional inhibitory transmission.

Main Methods:

• Spinal cord transection at the thoracic level on postnatal day 0 (P0) in rats to eliminate brain stem influence.
• Electrophysiological recordings to measure E(IPSP) in lumbar motoneurons at postnatal days 4-7 (P4-P7).
• K-Cl cotransporter KCC2 immunohistochemistry and functional assays (bumetanide sensitivity, potassium concentration changes) to assess KCC2 activity.

Main Results:

• E(IPSP) was significantly more depolarized in cord-transected animals compared to controls, resembling earlier developmental stages.
• Developmental increase in KCC2 staining in lumbar motoneurons was observed in intact animals but absent in cord-transected ones.
• Motoneurons in transected animals showed reduced sensitivity to KCC2 functional manipulations, including bumetanide and altered extracellular potassium.

Conclusions:

• Brain stem influences play a vital role in the maturation of inhibitory synaptic transmission in the spinal cord.
• These brain influences likely promote the upregulation and functionality of the KCC2 transporter, facilitating the shift to inhibitory neurotransmission.