Abstract
The neurotrophin brain-derived neurotrophic factor (BDNF) is known to regulate synaptic plasticity and memory formation in the hippocampus and the neocortex of the mammalian brain. In contrast, a role of BDNF in mediating synaptic plasticity and fear learning in the amygdala is just beginning to evolve. Using patch clamp recordings from projection neurons of the dorsal lateral amygdala (LA) in acute slices of mice, we now investigated the cellular mechanism of BDNF-mediated long-term potentiation (LTP) of excitatory postsynaptic currents (EPSCs) in the amygdala. LTP was elicited in cortical and thalamic synaptic inputs by pairing postsynaptic depolarisation with presynaptic stimulation. LTP in the cortico-amygdala pathway was not changed in heterozygous BDNF-knockout (BDNF(+/-)) mice. In contrast, pairing induced LTP in the thalamic input was abolished in BDNF(+/-) mice (BDNF(+/-): 104.0 ± 5.7% of initial EPSC values; WT: 132.5 ± 7.3%). Likewise, inhibition of BDNF/TrkB signalling with TrkB-IgGs as scavenger molecules for endogenous BDNF blocked LTP in wild-type mice in this pathway (TrkB-IgG: 102.7 ± 6.9% of initial EPSC values; control: 132.5 ± 8.7%). Inclusion of the tyrosine kinase inhibitor K252a in the pipette solution also prevented the induction of LTP in the thalamic pathway, indicating a postsynaptic site of action of BDNF in regulating LTP. Reduced BDNF levels in BDNF(+/-) mice did not affect intrinsic membrane properties of LA projection neurons. Likewise, presynaptic glutamate release, and postsynaptic membrane properties also remained unaffected in BDNF(+/-) mice. These data suggest a postsynaptic site of action of BDNF in mediating LTP selectively in the thalamic fear conditioning pathway.