title: The basolateral amygdala γ-aminobutyric acidergic system in health and disease.
abstract: The brain comprises an excitatory/inhibitory neuronal network that maintains a finely tuned balance of activity critical for normal functioning. Excitatory activity in the basolateral amygdala (BLA), a brain region that plays a central role in emotion and motivational processing, is tightly regulated by a relatively small population of γ-aminobutyric acid (GABA) inhibitory neurons. Disruption in GABAergic inhibition in the BLA can occur when there is a loss of local GABAergic interneurons, an alteration in GABAA receptor activation, or a dysregulation of mechanisms that modulate BLA GABAergic inhibition. Disruptions in GABAergic control of the BLA emerge during development, in aging populations, or after trauma, ultimately resulting in hyperexcitability. BLA hyperexcitability manifests behaviorally as an increase in anxiety, emotional dysregulation, or development of seizure activity. This Review discusses the anatomy, development, and physiology of the GABAergic system in the BLA and circuits that modulate GABAergic inhibition, including the dopaminergic, serotonergic, noradrenergic, and cholinergic systems. We highlight how alterations in various neurotransmitter receptors, including the acid-sensing ion channel 1a, cannabinoid receptor 1, and glutamate receptor subtypes, expressed on BLA interneurons, modulate GABAergic transmission and how defects of these systems affect inhibitory tonus within the BLA. Finally, we discuss alterations in the BLA GABAergic system in neurodevelopmental (autism/fragile X syndrome) and neurodegenerative (Alzheimer's disease) diseases and after the development of epilepsy, anxiety, and traumatic brain injury. A more complete understanding of the intrinsic excitatory/inhibitory circuit balance of the amygdala and how imbalances in inhibitory control contribute to excessive BLA excitability will guide the development of novel therapeutic approaches in neuropsychiatric diseases.
authors.affiliation: Department of Anatomy, Physiology, and Genetics, F. Edward Hébert School of Medicine, Uniformed Services, University of the Health Sciences, Bethesda, Maryland.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Prager
authors.affiliation: Psychology Department, Vassar College, Poughkeepsie, New York.
authors.forename: Hadley C
authors.initials: HC
authors.lastname: Bergstrom
authors.affiliation: Center for the Study of Traumatic Stress, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland.|Department of Psychiatry, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland.|Program in Neuroscience, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
authors.forename: Gary H
authors.initials: GH
authors.lastname: Wynn
authors.affiliation: Department of Anatomy, Physiology, and Genetics, F. Edward Hébert School of Medicine, Uniformed Services, University of the Health Sciences, Bethesda, Maryland.|Center for the Study of Traumatic Stress, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland.|Department of Psychiatry, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland.|Program in Neuroscience, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
authors.forename: Maria F M
authors.initials: MF
authors.lastname: Braga
mesh_terms: D066272:Basolateral Nuclear Complex / Q000378:metabolism* / Q000473:pathology*; D001927:Brain Diseases / Q000150:complications* / Q000473:pathology*; D006801:Humans; D007395:Interneurons / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D005680:gamma-Aminobutyric Acid
keywords: Alzheimer's disease; GABA; anxiety; autism; basolateral amygdala; epilepsy