Cholesterol depletion inhibits BDNF-dependent spike timing-dependent plasticity at thalamo-amygdala synapses.
📄 Abstract
The neurotrophin brain-derived neurotrophic factor (BDNF) has emerged as a key regulator of synaptic plasticity in hippocampus and cortex of mammalian brains. In the lateral nucleus of the amygdala (LA), BDNF is involved in the control of long-term potentiation (LTP). Here, we show that BDNF is involved in spike-timing dependent potentiation (STDP) of thalamic inputs onto LA projection neurons. Inhibition of BDNF/TrkB signaling with the TrkB scavenger TrkB/FC completely blocked this timing-dependent form of LTP (t-LTP). Disruption of lipid-rafts by depletion of cholesterol from synaptic microdomains with Methyl-β-cyclodextrin (MCD) also prevented induction and expression of t-LTP. These data suggest that BDNF-induced TrkB translocation into synaptic lipid-rafts is required for induction of t-LTP at thalamo-amygdala synapses. Since cholesterol-dependent modulation is not unique for TrkB receptor signaling but has been described for other receptors and ion channels involved in synaptic plasticity, additional studies are required to obtain a more complete picture regarding their role in t-LTP at thalamo-amygdala afferents.