ArticleThe international journal of neuropsychopharmacology2021
Behavioral Deficits Induced by Somatostatin-Positive GABA Neuron Silencing Are Rescued by Alpha 5 GABA-A Receptor Potentiation.
Article in The international journal of neuropsychopharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- SST interneurons facilitate dendritic calcium signaling via tonic activation of α5-GABA receptors.Neuron · 2026Article
- Linking reduced prefrontal microcircuit inhibition in schizophrenia to EEG biomarkers in silico.PLoS computational biology · 2026Article
- Multiplexed changes in synaptic transmission underlie stress-induced reduction of persistent firing in the parietal cortex.Progress in neurobiology · 2026Article
- A Novel Polygenic Risk Score Indexing Somatostatin-Expressing Inhibitory Neurons Predicts Somatostatin-Expressing Cell Proportions and Severity of Symptoms in Late-Life Depression.Biological psychiatry global open science · 2026Article
- The synaptic triad in depression: how stress-related pathways converge on BDNF, NMDA receptor, and MMP-9.Pharmacological reports : PR · 2026Review
- Mutant huntingtin expression in somatostatin-positive interneurons contributes to neurophysiological and behavioral phenotypes in BACHD mice.Disease models & mechanisms · 2026Article
- Eukaryotic initiation factor 4E: a key factor of traumatic stress-induced depression-related cognitive decline at different age.Translational psychiatry · 2026Article
- Negative allosteric modulation of α5-GABAbioRxiv : the preprint server for biology · 2026Article
- GABADrug design, development and therapy · 2026Review
- Article
- Sex-specific GABAergic microcircuits that switch vulnerability into resilience to stress and reverse the effects of chronic stress exposure.Molecular psychiatry · 2025Article
- Spine loss in depression impairs dendritic signal integration in human cortical microcircuit models.iScience · 2025Article
- Electroencephalography Biomarkers of α5-GABA Positive Allosteric Modulators in Rodents.Biological psychiatry global open science · 2025Article
- A chronopharmacological comparison of ciprofol and propofol: focus on sedation and side effects.Frontiers in molecular neuroscience · 2025Article
- Therapeutic dose prediction of α5-GABA receptor modulation from simulated EEG of depression severity.PLoS computational biology · 2024Article
- Somatostatin: Linking Cognition and Alzheimer Disease to Therapeutic Targeting.Pharmacological reviews · 2024Review
- Large-Scale Mechanistic Models of Brain Circuits with Biophysically and Morphologically Detailed Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Review
- Sex-specific GABAergic microcircuits that switch vulnerability into resilience to stress and reverse the effects of chronic stress exposure.Research square · 2024Article
- In-silico testing of new pharmacology for restoring inhibition and human cortical function in depression.Communications biology · 2024Article
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Authors and funding
9 authors.
Funding
Abstract
introductionDeficits in somatostatin-positive gamma-aminobutyric acid interneurons (SST+ GABA cells) are commonly reported in human studies of mood and anxiety disorder patients. A causal link between SST+ cell dysfunction and symptom-related behaviors has been proposed based on rodent studies showing that chronic stress, a major risk factor for mood and anxiety disorders, induces a low SST+ GABA cellular phenotype across corticolimbic brain regions; that lowering Sst, SST+ cell, or GABA functions induces depressive-/anxiety-like behaviors (a rodent behavioral construct collectively defined as "behavioral emotionality"); and that disinhibiting SST+ cells has antidepressant-like effects. Recent studies found that compounds preferentially potentiating receptors mediating SST+ cell functions, α5-GABAA receptor positive allosteric modulators (α5-PAMs), achieved antidepressant-like effects. Together, the evidence suggests that SST+ cells regulate mood and cognitive functions that are disrupted in mood disorders and that rescuing SST+ cell function via α5-PAM may represent a targeted therapeutic strategy.
methodsWe developed a mouse model allowing chemogenetic manipulation of brain-wide SST+ cells and employed behavioral characterization 30 minutes after repeated acute silencing to identify contributions to symptom-related behaviors. We then assessed whether an α5-PAM, GL-II-73, could rescue behavioral deficits.
resultsBrain-wide SST+ cell silencing induced features of stress-related illnesses, including elevated neuronal activity and plasma corticosterone levels, increased anxiety- and anhedonia-like behaviors, and impaired short-term memory. GL-II-73 led to antidepressant- and anxiolytic-like improvements among behavioral deficits induced by brain-wide SST+ cell silencing.
conclusionOur data validate SST+ cells as regulators of mood and cognitive functions and demonstrate that bypassing low SST+ cell function via α5-PAM represents a targeted therapeutic strategy.
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