title: Gene-environment interactions in cortical interneuron development and dysfunction: A review of preclinical studies.
abstract: Cortical interneurons (cINs) are a diverse group of locally projecting neurons essential to the organization and regulation of neural networks. Though they comprise only ∼20% of neurons in the neocortex, their dynamic modulation of cortical activity is requisite for normal cognition and underlies multiple aspects of learning and memory. While displaying significant morphological, molecular, and electrophysiological variability, cINs collectively function to maintain the excitatory-inhibitory balance in the cortex by dampening hyperexcitability and synchronizing activity of projection neurons, primarily through use of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Disruption of the excitatory-inhibitory balance is a common pathophysiological feature of multiple seizure and neuropsychiatric disorders, including epilepsy, schizophrenia, and autism. While most studies have focused on genetic disruption of cIN development in these conditions, emerging evidence indicates that cIN development is exquisitely sensitive to teratogenic disruption. Here, we review key aspects of cIN development, including specification, migration, and integration into neural circuits. Additionally, we examine the mechanisms by which prenatal exposure to common chemical and environmental agents disrupt these events in preclinical models. Understanding how genetic and environmental factors interact to disrupt cIN development and function has tremendous potential to advance prevention and treatment of prevalent seizure and neuropsychiatric illnesses.
authors.affiliation: Department of Comparative Biosciences School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI, 53706, USA; Comparative Biomedical Sciences Graduate Program, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI, 53706, USA. Electronic address: ansenwilson@wisc.edu.
authors.forename: Lydia J
authors.initials: LJ
authors.lastname: Ansen-Wilson
authors.affiliation: Department of Comparative Biosciences School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI, 53706, USA; Comparative Biomedical Sciences Graduate Program, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI, 53706, USA; Molecular and Environmental Toxicology Center, School of Medicine and Public Health, University of Wisconsin-Madison, 1010B McArdle Building, 1400 University Avenue, Madison, WI, 53706, USA. Electronic address: robert.lipinski@wisc.edu.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lipinski
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology*; D059647:Gene-Environment Interaction; D006801:Humans; D007395:Interneurons / Q000502:physiology*; D001523:Mental Disorders / Q000209:etiology / Q000235:genetics / Q000473:pathology; D012640:Seizures / Q000209:etiology / Q000235:genetics / Q000473:pathology; D057170:Translational Research, Biomedical
keywords: Cortical development; Developmental neurotoxicity; Gene-environment; Interneuron; Schizophrenia; Seizure