The "psychiatric" neuron: the psychic neuron of the cerebral cortex, revisited

Abstract

Nearly 25 years ago, Dr. Patricia Goldman-Rakic published her review paper, "The 'Psychic' Neuron of the Cerebral Cortex," outlining the circuit-level dynamics, neurotransmitter systems, and behavioral correlates of pyramidal neurons in the cerebral cortex, particularly as they relate to working memory. In the decades since the release of this paper, the existing literature and our understanding of the pyramidal neuron have increased tremendously, and research is still underway to better characterize the role of the pyramidal neuron in both healthy and psychiatric disease states. In this review, we revisit Dr. Goldman-Rakic's characterization of the pyramidal neuron, focusing on the pyramidal neurons of the prefrontal cortex (PFC) and their role in working memory. Specifically, we examine the role of PFC pyramidal neurons in the intersection of working memory and social function and describe how deficits in working memory may actually underlie the pathophysiology of social dysfunction in psychiatric disease states. We briefly describe the cortico-cortical and corticothalamic connections between the PFC and non-PFC brain regions, as well the microcircuit dynamics of the pyramidal neuron and interneurons, and the role of both these macro- and microcircuits in the maintenance of the excitatory/inhibitory balance of the cerebral cortex for working memory function. Finally, we discuss the consequences to working memory when pyramidal neurons and their circuits are dysfunctional, emphasizing the resulting social deficits in psychiatric disease states with known working memory dysfunction.

Keywords: ADHD; Psychic cells; anxiety; mental disorders; prefrontal cortex; schizophrenia; social behavior; working memory.

Figure 1

Schematic representation of the functional circuits involved in working memory. Anatomical (solid black line) and functional (dashed green line) connections between brain regions are represented by arrows, with arrowheads indicating the direction of the connection. Specific circuits highlighted include VTA to PFC (direct, reciprocal); vHC to PFC (direct) and dHC to PFC (indirect/multisynaptic); PFC to RE (direct, reciprocal) and RE to dHC (direct, reciprocal); PFC to MD (direct, reciprocal); VC to PFC (indirect/multisynaptic); and AC to PFC (indirect/multisynaptic). PFC, prefrontal cortex; dHC, dorsal hippocampus; vHC, ventral hippocampus; RE, nucleus reuniens, MD, mediodorsal thalamus; VC, visual cortex; AC, auditory cortex; VTA, ventral tegmental area.

Figure 2

Schematic representation of PFC microcircuitry. Diagram depicting the microcircuitry of the pyramidal neuron (PN) with each of the three interneuron (IN) subtypes. Parvalbumin-expressing INs (PV) inhibit PNs that are not tuned to the relevant receptive field. Somatostatin-expressing INs (SST) inhibit PNs, and their activity is associated with the delay period of working memory (WM) tasks. Vasoactive intestinal peptide-expressing INs (VIP) inhibit PV and SST INs, thus disinhibiting PNs.