Functional expression of TrkB receptors on interneurones and pyramidal cells of area CA3 of the rat hippocampus

Abstract

The dentate gyrus and hippocampal area CA3 region of the mammalian brain contains the highest levels of brain-derived neurotrophic factor (BDNF) and its canonical membrane receptor, tropomyosin-related kinase B (TrkB). Therefore, the present study examines the expression and physiological responses triggered by activation of TrkB on hippocampal area CA3 interneurones and pyramidal cells of the rat hippocampus. Triple immunolabelling for TrkB, glutamate decarboxylase 67, and the calcium-binding proteins parvalbumin, calbindin or calretinin confirms the somatic expression of TrkB in all CA3 sublayers. TrkB-positive interneurones with fast-spiking discharge are restricted to strata oriens and lucidum, whereas regular-spiking interneurones are found in the strata lucidum, radiatum and lacunosum-moleculare. Activation of TrkB receptors with 7,8-dihydroxyflavone (DHF) modulates amplitude and frequency of spontaneous synaptic currents recorded from CA3 interneurones. Furthermore, the isolated excitatory postsynaptic currents (EPSC) of CA3 interneurones evoked by the mossy fibres (MF) or commissural/associational (C/A) axons, show input-specific synaptic potentiation in response to TrkB stimulation. On CA3 pyramidal cells, stimulation with DHF potentiates the MF synaptic transmission and increases the MF-EPSP – spike coupling. The latter exhibits a dramatic increase when picrotoxin is bath perfused after DHF, indicating that local interneurones restrain the excitability mediated by activation of TrkB. Therefore, we propose that release of BDNF on area CA3 reshapes the output of this hippocampal region by simultaneous activation of TrkB on GABAergic interneurones and pyramidal cells.