# Cholesterol depletion inhibits BDNF-dependent spike timing-dependent plasticity at thalamo-amygdala synapses

## TL;DR

This study shows that cholesterol depletion blocks a type of brain cell communication in the amygdala that depends on BDNF and timing of electrical signals.

## Contribution

The study reveals a novel role for cholesterol and BDNF in timing-dependent synaptic plasticity in the amygdala.

## Key findings

- BDNF is involved in timing-dependent long-term potentiation (t-LTP) at thalamo-amygdala synapses.
- Cholesterol depletion prevents t-LTP induction and expression by disrupting BDNF/TrkB signaling.
- TrkB translocation into lipid rafts is necessary for t-LTP at these 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.