Layer V pyramidal neurons are also afflicted in schizophrenia (Black et al., 2004) and in AD (Bussière et al., 2003) and may contribute to symptoms. For example, alterations in corollary discharge feedback from the PFC are thought to contribute to symptoms of hallucinations (Ford et al., 2002), and errors in feedback may also play a role in delusions (Corlett et al., 2007). Thus, this aspect of dlPFC function deserves further investigation. The dlPFC expands greatly over evolution, with no exact counterpart in rodents, and an enormous extension

from nonhuman to human primates (Elston, 2003; Elston et al., 2006; Preuss, 1995; Wise, 2008). Comparisons of dendritic complexity in human versus animal cortices have shown that the basal dendrites of dlPFC deep layer III AZD5363 in vitro pyramidal cells are the ones most increased in primate evolution,

with increases in both dendritic complexity and the number of spines (Elston, 2003). Layer III pyramidal cells in the dlPFC have many more spines than do their counterparts in primary visual cortex (V1); for example, there is an average of 16 times more spines in rhesus dlPFC and 23 times more spines in the human dlPFC (Elston, 2000). Elston (2003) quotes the initial observations of Ramón y Cajal, who first noted these evolutionary changes in pyramidal cells, which he termed “psychic” cells due to their likely function: “In mice the basal dendrites [of pyramidal cells] are short and have few branches,

in man find more they [the basal dendrites] are numerous, long and highly branched . . . as one ascends the animal scale the psychic cell becomes larger and more complex; it’s natural to attribute this progressive morphological complexity, in part at least, to its progressive functional state.” Or, as Elston concludes: “without these specializations in the structure Sodium butyrate of pyramidal cells, and the circuits they form, human cognitive processing would not have evolved to its present state. The working memory “mental sketch pad” differs from long-term memory consolidation in a number of elementary ways. Working memory is a momentary (timescale of seconds), ever-changing pattern of recurrent activation of relatively stable architectural networks (Figure 2A), while long-term memory consolidation retains events as structural changes in synapses (Figure 2B). Long-term plastic changes begin with relatively rapid alterations in the numbers of AMPA and NMDA receptors in the synapse (Lüscher and Malenka, 2012), leading to structural changes, such as enlarging of the spine head and shortening/thickening of the spine neck (Yuste and Bonhoeffer, 2001) to create a stable, mushroom-shaped spine and enduring strengthening of a synaptic connection (Araya et al., 2006) (Figure 2B), and/or the addition of new spines and synapses (Yuste and Bonhoeffer, 2001).