The “Psychic” Neuron of the Cerebral Cortex

ABSTRACT: Remarkable advances in the identification, cloning, and localization of ion channels and receptors in the central nervous system have opened up unprecedented possibilities for relating structure to physiological function at the subcellular level of analysis. A singularly advanced property of select central nervous system neurons is their ability to exhibit increases in firing rate in relation to the mnemonic trace of a preceding event, a property that has been referred to as “working memory.” Single‐cell recordings from the prefrontal cortex of nonhuman primates have revealed neurons in the prefrontal cortex that possess “memory fields” analogous to the receptive field properties of sensory neurons. The integrity of these neurons has been shown to be essential for accurate performance in memory tasks performed by trained monkeys (and humans). We can now show that the excitability and/or tuning of these prefrontal neurons are subject to modulatory influences by dopamine, serotonin, GABA, and glutamate among other peptides and conventional neurotransmitters. I will describe the dopaminergic, serotonergic, and GABAergic innervation of pyramidal neurons engaged in working memory and the localization of neurotransmitter receptors through which they exert their actions. The findings reveal a remarkable degree of diversity in the subcellular localization and functionality of the five cloned dopamine receptors (D1, D2, D3, D4, and D5) and two serotonin (5HT2A and 5HT3) receptors that have been examined to date. The potential now exists for linking systems neurobiology with molecular biophysics to comprehend the highest functions of information processing that distinguish our species.