Abstract
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.
Highlights
The cortico-hippocampal circuit is implicated in the formation, storage, and retrieval of spatial and episodic memories (Lisman, 1999)
Because dendritic Na+ channels could generate local spikes that were independent of axosomatic AP generation and were not affected by voltage attenuation, we suggest that Na+ spikes in the dendrites provide the postsynaptic signal necessary for the induction of long-term potentiation (LTP) at PP-granule cells (GCs) synapses
We examined GCs with an input resistance (Rin)
Summary
The cortico-hippocampal circuit is implicated in the formation, storage, and retrieval of spatial and episodic memories (Lisman, 1999). Theoretical models of hippocampal function propose that the DG is critically involved in pattern separation and that synaptic transmission and plasticity at PP-granule cell (GC) synapses in the DG is required to remove redundant memory representations (Marr, 1971; McNaughton and Morris, 1987; Treves and Rolls, 1994). In agreement with theoretical predictions, knockout of Nmethyl-D-aspartate (NMDA) receptors in GCs impairs long-term potentiation (LTP) and the ability to rapidly form a contextual representation and discriminate it from previous similar memories in a contextual fear conditioning task (McHugh et al, 2007). GCs that were activated by contextual fear conditioning, referred to as memory engram cells, present clear signatures of synaptic potentiation such as a larger AMPA-NMDA ratio and a greater density of dendritic spines (Ryan et al, 2015). Knowledge of plasticity at PP-GC synapses is essential for understanding the hippocampal function
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