Understanding GABAergic synapse diversity and its implications for GABAergic pharmacotherapy DOI Creative Commons
Dilja Krueger‐Burg

Trends in Neurosciences, Journal Year: 2025, Volume and Issue: 48(1), P. 47 - 61

Published: Jan. 1, 2025

Despite the substantial contribution of disruptions in GABAergic inhibitory neurotransmission to etiology psychiatric, neurodevelopmental, and neurodegenerative disorders, surprisingly few drugs targeting system are currently available, partly due insufficient understanding circuit-specific synapse biology. In addition GABA receptors, synapses contain an elaborate organizational protein machinery that regulates properties synaptic transmission. Until recently, this remained largely unexplored, but key methodological advances have now led identification a wealth new organizer proteins. Notably, many these proteins appear function only at specific subsets synapses, creating diversity complexes may serve as targets for pharmacotherapies. The present review aims summarize developments underlie newfound knowledge provide current overview synapse-specific complexes, well outlining future avenues challenges translating into clinical applications.

Language: Английский

GluN3A excitatory glycine receptors control adult cortical and amygdalar circuits DOI Creative Commons
Simon Bossi, Dhanasak Dhanasobhon, Graham C. R. Ellis‐Davies

et al.

Neuron, Journal Year: 2022, Volume and Issue: 110(15), P. 2438 - 2454.e8

Published: June 13, 2022

GluN3A is an atypical glycine-binding subunit of NMDA receptors (NMDARs) whose actions in the brain are mostly unknown. Here, we show that expression subunits controls excitability mouse adult cortical and amygdalar circuits via unusual signaling mechanism involving formation excitatory glycine GluN1/GluN3A (eGlyRs) their tonic activation by extracellular glycine. eGlyRs extrasynaptic reside specific neuronal populations, including principal cells basolateral amygdala (BLA) SST-positive interneurons (SST-INs) neocortex. In BLA, eGlyR currents sensitive to fear-conditioning protocols, subject neuromodulation dopaminergic system, control stability fear memories. neocortex, vivo spiking SST-INs behavior-dependent modulation activity. GluN3A-containing thus represent a novel widespread modality brain, with attributes strikingly depart from those conventional NMDARs.

Language: Английский

Citations

39
Mapping visual functions onto molecular cell types in the mouse superior colliculus DOI Creative Commons
Yuanming Liu, Élise Savier,

Victor J. DePiero

et al.

Neuron, Journal Year: 2023, Volume and Issue: 111(12), P. 1876 - 1886.e5

Published: April 21, 2023

The superficial superior colliculus (sSC) carries out diverse roles in visual processing and behaviors, but how these functions are delegated among collicular neurons remains unclear. Here, using single-cell transcriptomics, we identified 28 neuron subtypes subtype-enriched marker genes from tens of thousands adult mouse sSC neurons. We then asked whether the sSC's molecular tuned to different stimuli. Specifically, imaged calcium dynamics single vivo during stimulation mapped gene transcripts onto same ex vivo. Our results identify a subtype inhibitory accounting for ∼50% direction-selective cells, suggesting genetic logic functional organization sSC. In addition, our studies provide comprehensive atlas multimodal mapping method that will facilitate investigation their respective functions, connectivity, development.

Language: Английский

Citations

36
Improvement of sensory deficits in fragile X mice by increasing cortical interneuron activity after the critical period DOI Creative Commons
Nazim Kourdougli, Anand Suresh, Benjamin Liu

et al.

Neuron, Journal Year: 2023, Volume and Issue: 111(18), P. 2863 - 2880.e6

Published: July 13, 2023

Changes in the function of inhibitory interneurons (INs) during cortical development could contribute to pathophysiology neurodevelopmental disorders. Using all-optical vivo approaches, we find that parvalbumin (PV) INs and their immature precursors are hypoactive transiently decoupled from excitatory neurons postnatal mouse somatosensory cortex (S1) Fmr1 KO mice, a model fragile X syndrome (FXS). This leads loss (PV-INs) both mice humans with FXS. Increasing activity future PV-INs neonatal restores PV-IN density ameliorates transcriptional dysregulation S1, but not circuit dysfunction. Critically, administering an allosteric modulator Kv3.1 channels after S1 critical period does rescue dynamics tactile defensiveness. Symptoms FXS related disorders be mitigated by targeting PV-INs.

Language: Английский

Citations

30
Network state transitions during cortical development DOI
M. Wu, Nazim Kourdougli, Carlos Portera‐Cailliau

et al.

Nature reviews. Neuroscience, Journal Year: 2024, Volume and Issue: 25(8), P. 535 - 552

Published: May 23, 2024

Language: Английский

Citations

16
Understanding GABAergic synapse diversity and its implications for GABAergic pharmacotherapy DOI Creative Commons
Dilja Krueger‐Burg

Trends in Neurosciences, Journal Year: 2025, Volume and Issue: 48(1), P. 47 - 61

Published: Jan. 1, 2025

Despite the substantial contribution of disruptions in GABAergic inhibitory neurotransmission to etiology psychiatric, neurodevelopmental, and neurodegenerative disorders, surprisingly few drugs targeting system are currently available, partly due insufficient understanding circuit-specific synapse biology. In addition GABA receptors, synapses contain an elaborate organizational protein machinery that regulates properties synaptic transmission. Until recently, this remained largely unexplored, but key methodological advances have now led identification a wealth new organizer proteins. Notably, many these proteins appear function only at specific subsets synapses, creating diversity complexes may serve as targets for pharmacotherapies. The present review aims summarize developments underlie newfound knowledge provide current overview synapse-specific complexes, well outlining future avenues challenges translating into clinical applications.

Language: Английский

Citations

1