GABAergic transmission in the amygdala modulates the expression of anxiety. Understanding the interplay between GABAergic transmission and excitatory circuits in the amygdala is, therefore, critical for understanding the neurobiological basis of anxiety. Here, we used a multi-disciplinary approach to demonstrate that GluR5-containing kainate receptors regulate local inhibitory circuits, modulate the excitatory transmission from the basolateral amygdala to the central amygdala, and control behavioral anxiety. Genetic deletion of GluR5 or local injection of a GluR5 antagonist into the basolateral amygdala increases anxiety-like behavior. Activation of GluR5 selectively depolarized inhibitory neurons, thereby increasing GABA release and contributing to tonic GABA current in the basolateral amygdala. The enhanced GABAergic transmission leads to reduced excitatory inputs in the central amygdala. Our results suggest that GluR5 is a key regulator of inhibitory circuits in the amygdala and highlight the potential use of GluR5-specific drugs in the treatment of pathological anxiety.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1766473 | PMC |
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0000167 | PLOS |
Proc Natl Acad Sci U S A
January 2025
Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405.
Dysregulation of GABAergic inhibition is associated with pathological pain. Consequently, enhancement of GABAergic transmission represents a potential analgesic strategy. However, therapeutic potential of current GABA agonists and modulators is limited by unwanted side effects.
View Article and Find Full Text PDFTrends Neurosci
January 2025
Laboratory of Cell Biology and Neuroscience, Institute of Anatomy, University Medical Center of the Johannes Gutenberg University Mainz, Duesbergweg 6, 55128 Mainz, Germany. Electronic address:
Despite the substantial contribution of disruptions in GABAergic inhibitory neurotransmission to the etiology of psychiatric, neurodevelopmental, and neurodegenerative disorders, surprisingly few drugs targeting the GABAergic system are currently available, partly due to insufficient understanding of circuit-specific GABAergic synapse biology. In addition to GABA receptors, GABAergic synapses contain an elaborate organizational protein machinery that regulates the properties of synaptic transmission. Until recently, this machinery remained largely unexplored, but key methodological advances have now led to the identification of a wealth of new GABAergic organizer proteins.
View Article and Find Full Text PDFEur J Nucl Med Mol Imaging
January 2025
Department of Nuclear Medicine, Xiangya Hospital, Central South University, Changsha, 410008, P.R. China.
Purpose: Temporal lobe epilepsy (TLE) is a brain network disorder closely associated with synaptic loss and has a genetic basis. However, the in vivo whole-brain synaptic changes at the network-level and the underlying gene expression patterns in patients with TLE remain unclear.
Methods: In this study, we utilized a positron emission tomography with the synaptic vesicle glycoprotein 2 A radioligand [F]SynVesT-1 cohort and two independent transcriptome datasets to investigate the topological properties of the synaptic density similarity network (SDSN) in TLE and its correlation with significantly dysregulated risk genes.
Nutrients
December 2024
Department of Molecular Medicine, School of Medicine, Ewha Womans University, Seoul 07804, Republic of Korea.
: Sleep, a process physiologically vital for mental health, faces disruptions in various sleep disorders linked to metabolic and neurodegenerative risks. seed (Zizy) has long been recognized for its diverse pharmacological attributes, including analgesic, sedative, insomnia, and anxiety alleviation. : In this study, the sleep-prolonging effects of Zizy extract (100, 200 mg/kg), along with their characterizing compounds jujuboside A (JuA) (5, 10 mg/kg), were evaluated in a mouse model under a pentobarbital-induced sleep.
View Article and Find Full Text PDFGenes (Basel)
December 2024
Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA.
Background: (absent, small, or homeotic-like 1), a histone methyltransferase, has been identified as a high-risk gene for autism spectrum disorder (ASD). We previously showed that postnatal severe deficiency in the prefrontal cortex (PFC) of male and female mice caused seizures. However, the synaptic mechanisms underlying autism-like social deficits and seizures need to be elucidated.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!