Dendritic spikes in hippocampal granule cells are necessary for long-term potentiation at the perforant path synapse

Long-term potentiation (LTP) of synaptic responses is essential for hippocampal memory function. Perforant-path (PP) synapses on hippocampal granule cells (GCs) contribute to the formation of associative memories, which are considered the cellular correlates of memory engrams. However, the mechanisms of LTP at these synapses are not well understood. Due to sparse firing activity and the voltage attenuation in their dendrites, it remains unclear how associative LTP at distal synapses occurs. Here, we show that NMDA receptor-dependent LTP can be induced at PP-GC synapses without backpropagating action potentials (bAPs) in acute rat brain slices. Dendritic recordings reveal substantial attenuation of bAPs as well as local dendritic Na⁺ spike generation during PP-GC input. Inhibition of dendritic Na⁺ spikes impairs LTP induction at PP-GC synapse. These data suggest that dendritic spikes may constitute a key cellular mechanism for memory formation in the dentate gyrus.