Brain-derived neurotrophic factor drives the changes in excitatory synaptic transmission in the rat superficial dorsal horn that follow sciatic nerve injury

Lu, V, Biggs, J, Stebbing, M, Balasubramanyan, S, Todd, K, Lai, A, Colmers, W, Dawbarn, D, Ballanyi, K and Smith, P 2009, 'Brain-derived neurotrophic factor drives the changes in excitatory synaptic transmission in the rat superficial dorsal horn that follow sciatic nerve injury', Journal of Physiology, vol. 587, no. 5, pp. 1013-1032.


Document type: Journal Article
Collection: Journal Articles

Title Brain-derived neurotrophic factor drives the changes in excitatory synaptic transmission in the rat superficial dorsal horn that follow sciatic nerve injury
Author(s) Lu, V
Biggs, J
Stebbing, M
Balasubramanyan, S
Todd, K
Lai, A
Colmers, W
Dawbarn, D
Ballanyi, K
Smith, P
Year 2009
Journal name Journal of Physiology
Volume number 587
Issue number 5
Start page 1013
End page 1032
Total pages 19
Publisher Wiley-Blackwell Publishing, Inc
Abstract Peripheral nerve injury can promote neuropathic pain. The basis of the 'central sensitization' that underlies this often intractable condition was investigated using 14-20 day chronic constriction injury (CCI) of the sciatic nerve of 20-day-old rats followed by electrophysiological analysis of acutely isolated spinal cord slices. In addition, defined-medium organotypic spinal cord slice cultures were exposed for 5-6 days to brain-derived neurotrophic factor (BDNF, 200 ng ml-1) or to medium conditioned with activated microglia (aMCM). Since microglial activation is an early consequence of CCI, the latter manipulation allowed us to model the effect of peripheral nerve injury on the dorsal horn in vitro. Using whole-cell recording from superficial dorsal horn neurons, we found that both BDNF and CCI increased excitatory synaptic drive to putative excitatory `radial delay¿ neurons and decreased synaptic excitation of inhibitory 'tonic islet/central' neurons. BDNF also attenuated synaptic excitation of putative GABAergic neurons identified by glutamic acid decarboxylase (GAD) immunoreactivity. Intrinsic neuronal properties (rheobase, input resistance and action potential discharge rates) were unaffected. Exposure of organotypic cultures to either BDNF or aMCM increased overall excitability of the dorsal horn, as seen by increased cytoplasmic Ca2+ responses to 35 mm K+ as monitored by confocal Fluo-4AM imaging. The effect of aMCM was attenuated by the recombinant BDNF binding protein TrkBd5 and the effect of BDNF persisted when GABAergic inhibition was blocked with SR95531. These findings suggest that CCI enhances excitatory synaptic drive to excitatory neurons but decreases that to inhibitory neurons. Both effects are mediated by nerve injury-induced release of BDNF from microglia.
Subject Sensory Systems
DOI - identifier 10.1113/jphysiol.2008.166306
Copyright notice © 2009 The Authors. Journal compilation © 2009 The Physiological Society.
ISSN 0022-3751
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