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.
ABSTRACT
Understanding perturbations in synaptic function between health and disease states is crucial to the treatment of neuropsychiatric illness. While genome-wide association studies have identified several genetic loci implicated in synaptic dysfunction in disorders such as autism and schizophrenia, many have not been rigorously characterized. Here, we highlight immunoglobulin superfamily member 9b (IgSF9b), a cell adhesion molecule thought to localize exclusively to inhibitory synapses in the brain. While both pre-clinical and clinical studies suggest its association with psychiatric diseases, our understanding of IgSF9b in synaptic maintenance, neural circuits, and behavioral phenotypes remains rudimentary. Moreover, these functions wield undiscovered influences on neurodevelopment. This review evaluates current literature and publicly available gene expression databases to explore the implications of IgSF9b dysfunction in rodents and humans. Through a focused analysis of one high-risk gene locus, we identify areas requiring further investigation and unearth clues related to broader mechanisms contributing to the synaptic etiology of psychiatric disorders.
