Proceedings of The Physiological Society
Cardiff University (2009) Proc Physiol Soc 17, PC02
Long-term actions of BDNF on inhibitory synaptic transmission in identified neurons of the rat Substantia gelatinosa
P. A. Smith1, V. B. Lu2
1. Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada. 2. Laboratory of Neuropharmacology, NIH/NIAAA, Rockville, Maryland, United States.
Peripheral nerve injury promotes the release of brain derived neurotrophic factor (BDNF) from spinal microglial cells and primary afferent terminals (Coull et al., 2005). This induces a series of changes in the properties of neurons in the dorsal horn that lead to the ‘central sensitization’ that underlies neuropathic pain (Merighi et al.,2008). Several lines of evidence implicate the impairment of GABAergic and/or glycinergic inhibition in this process (Coull et al., 2005). To test this possibility further, we used a defined medium organotypic culture of rat spinal cord to examine changes in inhibitory synaptic transmission in substantia gelatinosa following 6d exposure to BDNF (200ng/ml). This duration of exposure seeks to mimic the prolonged increase in dorsal horn BDNF levels that accompany peripheral nerve injury. We used morphological and electrophysiological criteria as well as glutamic acid decarboxylase (GAD) immunohistochemistry to distinguish putative inhibitory neurons from putative excitatory neurons. Spontaneous IPSCs (sIPSCs) were recorded by means of whole-cell recording. BDNF exerted both pre- and postsynaptic effects on inhibitory synaptic transmission that were selective for neuron type. In putative excitatory ‘delay’ firing neurons, it increased sIPSC amplitude from 49.3±1.5 to 64.8±1.7pA (P<0.001), interevent interval (IEI) was reduced from 1089.9±34.7 to 776.4±18.3ms (P<0.01). In ‘tonic’ firing, putative inhibitory neurons, BDNF had little effect on sIPSC amplitude (67.6±1.9pA in control, 67.1±2.6pA in BDNF, ns). It did however increase IEI from 780.1±16.1 to 1174.7±37.8ms (P<0.001). Increased inhibitory drive to excitatory neurons and decreased inhibitory drive to inhibitory neurons seem inconsistent with our previous observation that BDNF increases overall dorsal horn excitability(Lu et al., 2007;Lu et al., 2009). Our results also contrast with published findings in Lamina I where impairment of inhibition may play a major role in central sensitization and/or the actions of BDNF (Coull et al., 2005). It is therefore suggested that central sensitization at the level of the substantia gelatinosa may reflect previously documented BDNF-induced increases in excitatory transmission (Lu et al., 2007;Lu et al., 2009)rather than decreases in inhibitory transmission.
Where applicable, experiments conform with Society ethical requirements