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 gamma-aminobutyric acid (GABA) inhibitory neurons. Disruption in GABAergic inhibition in the BLA can occur when there is a loss of local GABAergic interneurons, alterations in GABAA receptor activation, or dysregulation of mechanisms that modulate BLA GABAergic inhibition. Disruptions in GABAergic control of the BLA emerge during development, in aging populations, or after a trauma, ultimately resulting in hyperexcitability. BLA hyperexcitability manifests behaviorally as an increase in anxiety, emotional dysregulation, or the development of seizure activity. This article reviews 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 (ASIC1a), cannabinoid receptor 1 (CB1), and glutamate receptor subtypes, expressed on BLA interneurons, modulate GABAergic transmission and how defects of these systems affects 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.

Maturation changes the excitability and effective connectivity of the frontal lobe: A developmental TMS–EEG study

“…This region has been suggested to be related the cognitive control of sensorimotor functions (Zhang et al, ), and to be a part of a long‐range association limbic–motor pathway (Rizzo et al, ). Synaptic activity in the limbic circuits is tightly regulated by a relatively small population of GABA inhibitory neurons (Prager, Bergstrom, Wynn, & Braga, ) previously suggested to be involved in P180 genesis (Ferreri, Ponzo, et al, ; Salavati et al, ).…”

Receptor-driven, multimodal mapping of the human amygdala

“…Involvement of the basolateral nucleus in memory processing was dependent on cholinergic (Power et al 2003), GABAergic (Castellano et al 1989), adrenergic (Ferry et al 1999) and serotoninergic (Bombardi and Di Giovanni 2013) neurotransmission, as well as on interaction of neurotransmitter systems (Pare 2003;Rezayof et al 2011). Modulatory influences of glutamatergic, dopaminergic, serotoninergic, noradrenergic and cholinergic neurotransmission on the inhibitory tonus (GABAergic regulation) allow keeping an exquisite balance in the network activity of the basolateral nucleus (Prager et al 2016).…”

The efficacy of specific neuromodulators on human refractory chronic cough: a systematic review and meta-analysis

“…The GABAB receptor antagonist baclofen has been proved to suppress cough in cats with no effect on breathing pattern (13). Baclofen has shown good evidence that GABA8 receptors inhibit the activity of peripheral sensory afferent nerve fibers such as pulmonary C-fibers (14). GABAB receptor agonists have also been shown to possess antitussive effects in patients and in animals independent of their effects on transient lower esophageal sphincter relaxation (TLESR; the major cause of reflux) (15,16).…”

“…Use of baclofen to suppress cough induced by angiotensinconverting enzyme inhibitors and a diminished cough reflex has been associated with increased risk of developing aspiration pneumonia in stroke patients (14) and in the elderly (19). Gamma-aminobutyric acid (GABA), an inhibitory transmitter of the central nervous system, is also found in peripheral tissues, including the lungs (17).…”