Memory  >   NMDA Spikes and Plateaus Are Essential for Exciting Memory Engram Cells

It was thought that a neuron may fire action potentials if the excitatory postsynaptic potentials (EPSPs) generated at dendritic spines are sufficiently large so that their summation at the axon initial segment exceeds a threshold (Chapter 2). This concept assumes that EPSPs are the determining factor for the generation of action potentials. In the case of engram cells, however, this assumption is not true. The NMDA spike and plateau (Figure 8-1) resulting from glutamate stimulation play a more important role (Oikonomou et al., 2014).


Figure 8-1. Comparison among EPSP, NMDA spike and NMDA plateau. [Source: Oikonomou et al., 2012]

NMDA receptors (NMDARs) are located not only at synapses, but also widely distributed in the extrasynaptic membrane. The NMDA spike is a membrane potential change arising from synchronous activation of 10-50 neighboring synapses leading to the opening of NMDARs (Schiller et al., 2000; Antic et al., 2010). Repetitive clustered input can further produce the NMDA plateau (Oikonomou et al., 2012). Since the amplitudes of NMDA spike and plateau are larger than EPSP, they make important contribution to the generation of action potentials. In layer 5 pyramidal neurons, it has been shown that the EPSP generated by AMPA receptors (AMPARs) is too small to elicit action potentials. NMDA spikes in their basal dendrites are also required (Polsky et al., 2009).

The NMDA plateau initially starts as the NMDA spike, which depends not just on the temporal summation of membrane voltage, but primarily on the chemical summation of the glutamate originating from two sources: (1) synaptic spillover and (2) release from astrocytes. Once initiated, the glutamate-mediated NMDA plateau could not be interrupted by negative voltage pulses. Moreover, activation of extrasynaptic NMDARs in cellular compartments even without spines is sufficient to initiate and support NMDA plateaus. The only requirement is a surplus of free glutamate near a group of extrasynaptic receptors. (Oikonomou et al., 2012). Recently, it has also been shown that dendritic NMDA spikes are necessary for timing-dependent associative LTP in CA3 pyramidal cells (Brandalise et al., 2016).


Author: Frank Lee
First published: January, 2018
Last updated: April, 2018