|Memory Units, NMDA Spike and Plateau||Memory|
Accumulating evidence suggests that the preferred "memory unit" is not an individual synapse or spine. Rather, it may contain a cluster of synapses within the same dendritic branch (Govindarajan et al., 2006; Govindarajan et al., 2011; Kastellakis et al., 2015). These clustered synapses act synergistically to produce NMDA spike and NMDA plateau (Figure 10-1) to facilitate neuronal firing.
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; Chalifoux and Carter, 2011). Repetitive clustered input can further produce the NMDA plateau (Oikonomou et al., 2012). Since the amplitudes of NMDA spike and plateau are larger than excitatory postsynaptic potential (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 resembles the UP state of the slow oscillations that occur during deep sleep (Antic et al., 2010; Oikonomou et al., 2012). Importantly, action potentials are generated only in the UP state, not in the DOWN state (Figure 10-2), providing further evidence that NMDA plateaus are crucial for memory storing neurons to generate action potentials.
The clustered synapses capable of producing an NMDA plateau may form a memory unit. Thus, a memory unit could contain 10-50 synapses. Members of a memory unit are likely to change dynamically. In response to learning processes, new synapses could be added while existing synapses might be eliminated from a memory unit. A neuron may consist of multiple memory units, encoding similar or different objects and events. In the medial temporal lobe, each neuron was estimated to encode 50 - 150 distinct objects (Rey et al., 2015).
For simplicity, Figures 10-3 and 10-4 assume that the memory unit #1 contains only four synapses. Scattered input will generate EPSP which is insufficient to activate the memory unit. Only when the memory unit produces an NMDA plateau, can the unit be activated. Hence, memory extinction and retrieval could be fundamentally governed by the NMDA plateau. A memory unit would become extinguished (silenced) if it cannot produce an NMDA plateau at a given moment. Retrieval of a memory involving the unit requires the memory unit to produce an NMDA plateau first. Further details are discussed in subsequent chapters.
Author: Frank Lee