Cortex, Cognition and the Cell: New Insights into the Pyramidal Neuron and Prefrontal Function

Abstract

Arguably the most complex cortical functions are seated in human cognition, the how and why of which have been debated for centuries by theologians, philosophers and scientists alike. In his best-selling book, An Astonishing Hypothesis: A Scientific Search for the Soul, Francis Crick refined the view that these qualities are determined solely by cortical cells and circuitry. Put simply, cognition is nothing more, or less, than a biological function. Accepting this to be the case, it should be possible to identify the mechanisms that subserve cognitive processing. Since the pioneering studies of Lorent de Nó and Hebb, and the more recent studies of Fuster, Miller and Goldman-Rakic, to mention but a few, much attention has been focused on the role of persistent neural activity in cognitive processes. Application of modern technologies and modelling techniques has led to new hypotheses about the mechanisms of persistent activity. Here I focus on how regional variations in the pyramidal cell phenotype may determine the complexity of cortical circuitry and, in turn, influence neural activity. Data obtained from thousands of individually injected pyramidal cells in sensory, motor, association and executive cortex reveal marked differences in the numbers of putative excitatory inputs received by these cells. Pyramidal cells in prefrontal cortex have, on average, up to 23 times more dendritic spines than those in the primary visual area. I propose that without these specializations in the structure of pyramidal cells, and the circuits they form, human cognitive processing would not have evolved to its present state. I also present data from both New World and Old World monkeys that show varying degrees of complexity in the pyramidal cell phenotype in their prefrontal cortices, suggesting that cortical circuitry and, thus, cognitive styles are evolving independently in different species.

Specializations of the granular prefrontal cortex of primates: Implications for cognitive processing

“…While it is well known that neuron structure determines its biophysical properties (Koch, 1999), it is less well known how neuron structure may influence the functional properties of the circuits they compose. It is our contention that cortical circuits composed of pyramidal cells of different structure will be characterized by different functional capabilities, much in the same way that artificial systems composed of highly interconnected and powerful processors differ in their functional abilities to those composed of less powerful processors with fewer connections (for review, see Elston, 2003a). Several direct examples of the structure-function relationship have been demonstrated between pyramidal cell structure and cortical function.…”

“…Several direct examples of the structure-function relationship have been demonstrated between pyramidal cell structure and cortical function. For example, differences in the size of the dendritic trees of pyramidal cells potentially influence topographic sampling strategies and mixing of inputs (Jacobs and Scheibel, 2002;Elston, 2003a). Differences in the branching complexity in the Fig.…”

“…Reciprocity dictates that highly spinous neurons will receive more inputs than less spinous neurons, providing a basis for increased recurrent excitation (Wang, 2001;Jacobs and Scheibel, 2002;Elston, 2003a). However, very little is known of the diversity of these inputs.…”

“…Up to a 30-fold difference has been reported in the number of dendritic spines (the major postsynaptic sites of excitatory inputs) on neocortical pyramidal cells in the primate cerebral cortex . Because pyramidal cells comprise over 70% of all neurons in cortex (DeFelipe and Fariñ as, 1992), these dramatic differences in their structure are likely to influence not only cellular function, but the computational ability of the circuits they form (for reviews, see Shepherd and Greer, 1988;Churchland and Sejnowski, 1992;Koch, 1999;Mel, 1999;Segev et al, 2001;Elston, 2003aElston, , 2006Chklovskii et al, 2004;London and Hä usser, 2005). However, the Fig.…”

SLC25A12 expression is associated with neurite outgrowth and is upregulated in the prefrontal cortex of autistic subjects

“…11 Comparative studies of pyramidal neurons in granular prefrontal cortex have shown that human neurons display much larger dendritic trees and, on average, up to 20 times as many dendritic spines as those in the primary cortexes. 12,13 The maintenance of such dendritic complexity probably requires high levels of energy consumption. 14 We thought that SLC25A12 expression might be modified in prefrontal cortex pyramidal neurons in adult brain.…”