Presentation of trimethylthiazoline (TMT, a component of fox feces) to laboratory rats elicits freezing, a prominent behavioral sign of anxiety or fear. The present study investigated the neural basis of this unlearned response. Muscimol, a GABA A receptor agonist, was injected (4.4 nmol/0.5 l) into the bed nucleus of the stria terminalis (BNST) as well as into the amygdala, two brain areas known to be involved in anxiety and fear. Temporary inactivation of the BNST but not of the amygdala significantly blocked TMT-induced freezing. This effect was not caused by an enhancement of motor activity after BNST inactivation. In addition, these results confirm previous studies showing that freezing is possible despite amygdala inactivation. These results, and other findings in the literature, suggest that the BNST is critically involved in unlearned fear, whereas the amygdala is more involved in the acquisition and expression of learned fear.

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Non-technical summary Long-term potentiation (LTP) in the lateral amygdala (LA) is a widely accepted cellular correlate of fear learning. In the present study we analysed the involvement of the neurotrophin brain-derived neurotrophic factor (BDNF) in amygdala LTP by stimulating selectively thalamic or cortical sensory inputs into the LA. In heterozygous BDNF knockout mice we observed that LTP in the cortico-amygdala pathway remained intact, whereas LTP in the thalamo-amygdala pathway was abolished. Likewise, acute interference with BDNF/TrkB signalling in wild-type mice by application of a BDNF scavenger (TrkB-IgG) led to inhibition of LTP in this pathway. In addition, postsynaptic inhibition of TrkB receptors, which mediate BDNF effects, blocked LTP in the thalamic pathway. Thus, our data demonstrate for the first time a crucial role for postsynaptic BDNF signalling in mediating LTP selectively in the thalamo-amygdala pathway in the LA.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 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.