BDNF-mediated modulation of GABA and glycine release in dorsal horn lamina II from postnatal rats

Recent studies show that excitatoryglutamatergic transmission is potentiated by BDNF insuperficial dorsal horn, both at the pre- and the postsynapticsite. The role of BDNF in modulating GABA andglycine-mediated inhibitory transmission has not beenfully investigated. To determine whether the neurotrophinis effective in regulating the spontaneous release of thetwo neurotransmitters, we have recorded miniature inhibitorypostsynaptic currents (mIPSCs) in lamina II of postnatalrats. We show that application of BDNF enhancedthe spontaneous release of GABA and glycine, in presenceof tetrodotoxin. The effect was blocked by the trk-receptorinhibitor k-252a. Amplitude and kinetics of mIPSCswere not altered. Evoked GABA and glycine IPSCs(eIPSCs) were depressed by BDNF and the coefficient ofvariation of eIPSC amplitude was significantly increased.By recording glycine eIPSCs with the paired-pulse protocol,an increase of paired-pulse ratio during BDNF applicationwas observed. We performed parallel ultrastructuralstudies to unveil the circuitry involved in the effectsof BDNF. These studies show that synaptic interactionsbetween full length functional trkB receptors and GABAcontainingprofiles only occur at non peptidergic synapticglomeruli of types I and II. Expression of trkB in presynapticvesicle-containing dendrites originating fromGABAergic islet cells, indicates these profiles as key structuresin the modulation of inhibitory neurotransmissionby the neurotrophin. Our results thus describe a yetuncharacterized effect of BDNF in lamina II, giving furtherstrength to the notion that the neurotrophin plays animportant role in pain neurotransmission.