Retrograde GABA signaling adjusts sound localization by balancing excitation and inhibition in the brainstem.

Neuron

Department Biologie II, Division of Neurobiology, LMU Munich, Grosshadernerstrasse 2, 82152 Martinsried, Germany.

Published: July 2008

Central processing of acoustic cues is critically dependent on the balance between excitation and inhibition. This balance is particularly important for auditory neurons in the lateral superior olive, because these compare excitatory inputs from one ear and inhibitory inputs from the other ear to compute sound source location. By applying GABA(B) receptor antagonists during sound stimulation in vivo, it was revealed that these neurons adjust their binaural sensitivity through GABA(B) receptors. Using an in vitro approach, we then demonstrate that these neurons release GABA during spiking activity. Consequently, GABA differentially regulates transmitter release from the excitatory and inhibitory terminals via feedback to presynaptic GABA(B) receptors. Modulation of the synaptic input strength, by putative retrograde release of neurotransmitter, may enable these auditory neurons to rapidly adjust the balance between excitation and inhibition, and thus their binaural sensitivity, which could play an important role as an adaptation to various listening situations.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuron.2008.05.011DOI Listing

Publication Analysis

Top Keywords

excitation inhibition
12
balance excitation
8
auditory neurons
8
inputs ear
8
binaural sensitivity
8
gabab receptors
8
retrograde gaba
4
gaba signaling
4
signaling adjusts
4
adjusts sound
4

Similar Publications

Introduction: The (EMB) theory, a major causal hypothesis of autism (ASD: autism spectrum disorder), attributes excess androgens during early development as one of the causes. While studies have generally followed the EMB theory in females at birth, the co-occurrence of ASD in males at birth has been observed in conditions that are assumed to be associated with reduced androgen action during early development, including Klinefelter syndrome (KS) and sexual minorities. ASD is also associated with atypical sensory sensitivity, synesthesia, and savant syndrome.

View Article and Find Full Text PDF

Motion-less depth-selective optogenetic probe using tapered fiber and an electrically tuneable liquid crystal steering element.

Biomed Opt Express

January 2025

Center for Optics, Photonics and Lasers, Department of Physics, Engineering Physics and Optics, Université Laval, 2375 Rue de la Terrasse, Québec, Québec G1V 0A6, Canada.

A miniature electrically tuneable liquid crystal component is used to steer light from -1° to +1° and then to inject into a simple tapered fiber. This allows the generation of various propagation modes, their leakage, and selective illumination of the surrounding medium at different depth levels without using mechanical movements nor deformation. The performance of the device is characterized in a reference fluorescence medium (Rhodamine 6G) as well as in a mouse brain (medullary reticular formation and mesencephalic locomotor regions) during in-vivo experiments as a proof of concept.

View Article and Find Full Text PDF

Small molecule inhibits KCNQ channels with a non-blocking mechanism.

Nat Chem Biol

January 2025

Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.

Voltage-gated ion channels (VGICs) are crucial targets for neuropsychiatric therapeutics owing to their role in controlling neuronal excitability and the established link between their dysfunction and neurological diseases, highlighting the importance of identifying modulators with distinct mechanisms. Here we report two small-molecule modulators with the same chemical scaffold, Ebio2 and Ebio3, targeting a potassium channel KCNQ2, with opposite effects: Ebio2 acts as a potent activator, whereas Ebio3 serves as a potent and selective inhibitor. Guided by cryogenic electron microscopy, patch-clamp recordings and molecular dynamics simulations, we reveal that Ebio3 attaches to the outside of the inner gate, employing a unique non-blocking inhibitory mechanism that directly squeezes the S6 pore helix to inactivate the KCNQ2 channel.

View Article and Find Full Text PDF

Background: Alzheimer's disease (AD) is a serious neurodegenerative disorder without a clear understanding of pathophysiology. Recent experimental data have suggested neuronal excitation-inhibition (E-I) imbalance as an essential element of AD pathology, but E-I imbalance has not been systematically mapped out for either local or large-scale neuronal circuits in AD, precluding precise targeting of E-I imbalance in AD treatment.

Method: In this work, we apply a Multiscale Neural Model Inversion (MNMI) framework to the resting-state functional MRI data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to identify brain regions with disrupted E-I balance in a large network during AD progression.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!