Abstract
The computational repertoire of neurons is enhanced by regenerative electrical signals initiated in dendrites. These events, referred to as dendritic spikes, can act as cell-intrinsic amplifiers of synaptic input. Among these signals, dendritic NMDA spikes are of interest in light of their correlation with synaptic LTP induction. Because it is not possible to block NMDA spikes pharmacologically while maintaining NMDA receptors available to initiate synaptic plasticity, it remains unclear whether NMDA spikes alone can trigger LTP. Here we use dendritic recordings and calcium imaging to analyse the role of NMDA spikes in associative LTP in CA3 pyramidal cells. We show that NMDA spikes produce regenerative branch-specific calcium transients. Decreasing the probability of NMDA spikes reduces LTP, whereas increasing their probability enhances LTP. NMDA spikes and LTP occur without back-propagating action potentials. However, action potentials can facilitate LTP induction by promoting NMDA spikes. Thus, NMDA spikes are necessary and sufficient to produce the critical postsynaptic depolarization required for associative LTP in CA3 pyramidal cells.
Highlights
The computational repertoire of neurons is enhanced by regenerative electrical signals initiated in dendrites
This process is initiated by strong depolarization of the postsynaptic neuron, which activates NMDA (Nmethyl-D-aspartate) receptors and results in the calcium elevation that triggers the biochemical processes leading to long-term potentiation (LTP)
Are the NMDA spikes evoked by the ITDP protocol expressed in only one region of the dendritic tree or can multiple areas be implicated? We addressed this question by examining the EPSP/EPSC rise time as a proxy for the distance of the stimulated rCA3 inputs from the soma (Supplementary Fig. 5)
Summary
The computational repertoire of neurons is enhanced by regenerative electrical signals initiated in dendrites These events, referred to as dendritic spikes, can act as cell-intrinsic amplifiers of synaptic input. The Hebbian postulate, whereby a synapse is strengthened when presynaptic input is successful in evoking postsynaptic activity, is accepted as the basis for many forms of associative learning This process is initiated by strong depolarization of the postsynaptic neuron, which activates NMDA (Nmethyl-D-aspartate) receptors and results in the calcium elevation that triggers the biochemical processes leading to long-term potentiation (LTP). LTP can be induced at various synapses in the absence of bAPs5–13 In these studies, regenerative dendritic events referred to as dendritic spikes (dSpikes) may produce the depolarization needed to trigger LTP. Using a combination of electrophysiological and two-photon Ca2 þ imaging techniques, we identify dendritic NMDA spikes as the causal signal that initiates LTP at synapses between hippocampal CA3 pyramidal cells
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