Spinal cord transection enhances afferent-evoked inhibition in lamina II neurons and abolishes BDNF-induced facilitation of their sensory input.
We previously reported that the pronociceptive neurotrophin brain-derived neurotrophic factor (BDNF) induces facilitation of C-fiber evoked EPSCs and NMDA currents in lamina II neurons of rats up to P40. Here, patch-clamp recording was used to study BDNF-induced modification of synaptic and NMDA-evoked responses in transverse spinal slices from lumbar (L2-L5) spinal cord of rats from P3 to P21 following complete spinal cord transection at P2. After transection injury at either T13/L1 or L6/S1, BDNF failed to facilitate synaptic AMPA-kainate currents or agonist-induced NMDA currents. The evoked synaptic currents were smaller in amplitude, often consisting of a biphasic (excitatory-inhibitory) response. The EPSC decayed more rapidly in neurons from transected cords than in those from uninjured cords. In transected cords most neurons responded to the GABA(A) receptor antagonist bicuculline with a significant increase in duration of the excitatory synaptic response. This could subsequently be blocked by D-APV, suggesting an NMDA-receptor mediated component. These findings suggest that following spinal cord transection, BDNF spinal actions are no longer predominantly pronociceptive. It is possible that a diminished availability of full-length TrkB and an enhanced expression of truncated TrkB receptors in the injured cord could play an important role in reducing the effect of BDNF following injury. These data are compared to those obtained after contusion, and it is concluded that the physiological changes after spinal injury differ according to nature of the injury.
Garraway
Sandra M
SM
Department of Neurobiology and Behavior, State University of New York, Stony Brook, New York 11794, USA.
Mendell
Lorne M
LM
D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D004558:Electric Stimulation; D008159:Lumbar Vertebrae; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013119:Spinal Cord Injuries / Q000150:complications / Q000503:physiopathology*; D013376:Substantia Gelatinosa / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000502:physiology*; D013904:Thoracic Vertebrae
D019208:Brain-Derived Neurotrophic Factor; D016194:Receptors, N-Methyl-D-Aspartate