The neural circuits underlying brain function across cortical regions have expanded and changed greatly throughout evolution.  The most striking of these changes is in the prefrontal cortex, where even across primate species there has been dramatic expansion of dendritic arbor, spine density, circuit connections, and transmitter and receptor actions in layer III pyramidal cells through evolution.  These changes in circuit architecture and function are critical to our understanding of brain function and cognition.  One critical process reliant on prefrontal cortex is working memory, or holding information “in mind” in the absence of sensory input.  This talk will discuss what we know of the anatomy and physiology of the circuitry underlying spatial working memory, which are known to function differently from other cortical regions such as primary visual cortex.  Computational modeling has enhanced our understanding and guided future studies of these circuits, specifically in their dependence on activation of postsynaptic NMDA receptors containing NR2B subunits.  Recent work has also shown a transition in these circuits away from a gating role of AMPA receptors, which instead rely on cholinergic actions on nicotinic alpha7 receptors.  Additional data support unique regulatory actions of cAMP, gating ion channels such as HCN and KCNQ, and this regulation shows opposite actions to primary sensory cortices. Understanding the complex and unique actions of various receptors and ion channels on these complex circuits is a key area of research to inform more accurate computational models of prefrontal cortex and improve our understanding of the brain.

Session Chair: Murray Sherman