Theta Burst Firing Recruits BDNF Release and Signaling in Postsynaptic CA1 Neurons in Spike-Timing-Dependent LTP

•Distinct types of t-LTP are elicited by 1:1 and 1:4 modes of synaptic stimulation•The mechanism of 1:1 t-LTP is BDNF independent and switched off by 1:4 t-LTP•Endogenous postsynaptic BDNF mediates 1:4 t-LTP via AMPA receptor insertion•Imaging of postsynaptic BDNF reveals its secretion following STDP-like AP firing

SummaryTiming-dependent LTP (t-LTP) is a physiologically relevant type of synaptic plasticity that results from repeated sequential firing of action potentials (APs) in pre- and postsynaptic neurons. t-LTP can be observed in vivo and is proposed to be a cellular correlate of memory formation. While brain-derived neurotrophic factor (BDNF) is essential to high-frequency stimulation-induced LTP in many brain areas, the role of BDNF in t-LTP is largely unknown. Here, we demonstrate a striking change in the expression mechanism of t-LTP in CA1 of the hippocampus following two distinct modes of synaptic activation. Single postsynaptic APs paired with presynaptic stimulation activated a BDNF-independent canonical t-LTP. In contrast, a theta burst of postsynaptic APs preceded by presynaptic stimulation elicited BDNF-dependent postsynaptic t-LTP that relied on postsynaptic BDNF secretion. This suggests that BDNF release during burst-like patterns of activity typically observed in vivo may play a crucial role during memory formation.