Abstract
Brain-derived neurotrophic factor (BDNF) has previously been shown to play an important role in glutamatergic synaptic plasticity in the amygdala, correlating with cued fear learning. While glutamatergic neurotransmission is facilitated by BDNF signaling in the amygdala, its mechanism of action at inhibitory synapses in this nucleus is far less understood. We therefore analyzed the impact of chronic BDNF depletion on GABAA-mediated synaptic transmission in BDNF heterozygous knockout mice (BDNF+/−). Analysis of miniature and evoked inhibitory postsynaptic currents (IPSCs) in the lateral amygdala (LA) revealed neither pre- nor postsynaptic differences in BDNF+/− mice compared to wild-type littermates. In addition, long-term potentiation (LTP) of IPSCs was similar in both genotypes. In contrast, facilitation of spontaneous IPSCs (sIPSCs) by norepinephrine (NE) was significantly reduced in BDNF+/− mice. These results argue against a generally impaired efficacy and plasticity at GABAergic synapses due to a chronic BDNF deficit. Importantly, the increase in GABAergic tone mediated by NE is reduced in BDNF+/− mice. As release of NE is elevated during aversive behavioral states in the amygdala, effects of a chronic BDNF deficit on GABAergic inhibition may become evident in response to states of high arousal, leading to amygdala hyper-excitability and impaired amygdala function.
Highlights
Brain-derived neurotrophic factor (BDNF) signaling via its cognate TrkB receptor regulates differentiation and survival during neuronal maturation
GABAergic inhibitory postsynaptic currents (IPSCs) arising from local inhibitory interneurons were isolated in the presence of DNQX and AP5 to block glutamatergic transmission
Neither the rise time (10–90%; WT: 1.76 ± 0.13 ms, n = 9; BDNF+/−: 2.06 ± 0.22 ms, n = 9; p = 0.26) nor the decay time constant (τ; WT: 14.1 ± 1.2 ms, n = 9; BDNF+/−: 13.5 ± 0.9 ms, n = 9; p = 0.93) of Evoked IPSC (eIPSC) was different between genotypes (Figure 1B)
Summary
Brain-derived neurotrophic factor (BDNF) signaling via its cognate TrkB (tropomyosin-related kinase B) receptor regulates differentiation and survival during neuronal maturation. In many brain areas, facilitated by acute or chronic actions of BDNF via TrkB receptors, the role of BDNF signaling at inhibitory synapses seems to be more diverse [1,6,7]. Reduction of GABAergic tone may facilitate fear generalization, as well as the development of anxiety disorders [22,23] In line with this notion, amygdala hyper-excitability is a common phenomenon in disorders like epilepsy, anxiety, and stress-related diseases [24]. In the basal amygdala (BA), GABA release is facilitated via presynaptic α1A adrenergic receptors This mechanism, regulating neuronal excitability in the BA, is severely impaired by stress and attenuated after fear conditioning [25,26]
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