Ca(2+)-evoked synaptic transmission and neurotransmitter receptor levels are impaired in the forebrain of trkb (-/-) mice.

To determine the in vivo targets of long-lasting actions of TrkB signaling on synaptic function we analyze synaptic components of excitatory and inhibitory circuits in the cerebral cortex of trkB (-/-) mice. First, we show that K(+)-evoked glutamate and GABA release from forebrain mutant synaptosomes was decreased. Moreover, the dependence of regulated exocytosis on the SNARE SNAP-25 and the Ca(2+)-dependent neurotransmitter release were also impaired in trkB (-/-) mice. We also analyzed postsynaptic glutamate and GABA(A) ionotropic receptors in cortical areas of trkB mutant mice. By using Western blot we observed decreased levels of the AMPA receptor subunits GluR2/3 and GluR4 in trkB (-/-) forebrains. In contrast, the forebrain of mutant mice exhibited increased levels of the GABA(A) receptor subunit alpha3 and alpha5 and a reduction of the gamma2 subunit. Immunocytochemical analysis showed that the hippocampus and neocortex of mutant mice exhibited decreased numbers of interneurons positive for distinct AMPA and GABA(A) receptor subunits. Furthermore, alteration of inhibitory circuits in trkB (-/-) mice was also shown by the low expression of the GABA-synthesizing enzyme glutamic acid decarboxylase in mutant cortical areas. The present results indicate that long-lasting TrkB signaling is required for the precise adjustment of neurotransmitter release and for the correct composition of the fast glutamatergic and GABAergic receptor subunits in vivo.