Kv3 potassium currents mediate rapid repolarisation of action potentials (APs), supporting fast spikes and high repetition rates. Of the four Kv3 gene family members, Kv3.1 and Kv3.3 are highly expressed in the auditory brainstem and we exploited this to test for subunit-specific roles at the calyx of Held presynaptic terminal in the mouse. Deletion of Kv3.3 (but not Kv3.1) reduced presynaptic Kv3 channel immunolabelling, increased presynaptic AP duration and facilitated excitatory transmitter release; which in turn enhanced short-term depression during high-frequency transmission. The response to sound was delayed in the Kv3.3KO, with higher spontaneous and lower evoked firing, thereby reducing signal-to-noise ratio. Computational modelling showed that the enhanced EPSC and short-term depression in the Kv3.3KO reflected increased vesicle release probability and accelerated activity-dependent vesicle replenishment. We conclude that Kv3.3 mediates fast repolarisation for short precise APs, conserving transmission during sustained high-frequency activity at this glutamatergic excitatory synapse.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9110028 | PMC |
| http://dx.doi.org/10.7554/eLife.75219 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Ultrastructural Localization of Glutamate Delta Receptor 1 in the Rodent and Primate Lateral Habenula.
J Comp Neurol
January 2025
Graduate Program in Molecular and Systems Pharmacology, Emory University, Atlanta, Georgia, USA.
Glutamate delta receptor 1 (GluD1) is a unique synaptogenic molecule expressed at excitatory and inhibitory synapses. The lateral habenula (LHb), a subcortical structure that regulates negative reward prediction error and major monoaminergic systems, is enriched in GluD1. LHb dysfunction has been implicated in psychiatric disorders such as depression and schizophrenia, both of which are associated with GRID1, the gene that encodes GluD1.
View Article and Find Full Text PDFNeurocan regulates axon initial segment organization and neuronal activity.
Matrix Biol
January 2025
German Center for Neurodegenerative Diseases (DZNE), Helmholtz Association of German Research Centers, Magdeburg, Germany; Center for Behavioral Brain Sciences (CBBS), Magdeburg, Germany; Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany. Electronic address:
The neural extracellular matrix (ECM) accumulates in the form of perineuronal nets (PNNs), particularly around fast-spiking GABAergic interneurons in the cortex and hippocampus, but also around synapses and in association with the axon initial segments (AIS) and nodes of Ranvier. Increasing evidence highlights the role of Neurocan (Ncan), a brain-specific component of ECM, in the pathophysiology of neuropsychiatric disorders like bipolar disorder and schizophrenia. Ncan localizes at PNNs, perisynaptically, and at the nodes of Ranvier and the AIS, highlighting its potential role in regulating axonal excitability.
View Article and Find Full Text PDFTau association with synaptic mitochondria coincides with energetic dysfunction and excitatory synapse loss in the P301S tauopathy mouse model.
Neurobiol Aging
December 2024
University of Nebraska Medical Center, College of Medicine, Department of Neurological Sciences, Omaha, NE, USA. Electronic address:
Neurodegenerative Tauopathies are a part of several neurological disorders and aging-related diseases including, but not limited to, Alzheimer's Disease, Frontotemporal Dementia with Parkinsonism, and Chronic Traumatic Encephalopathy. The major hallmarks present in these conditions include Tau pathology (composed of hyperphosphorylated Tau tangles) and synaptic loss. in vivo studies linking Tau pathology and mitochondrial alterations at the synapse, an avenue that could lead to synaptic loss, remain predominantly scarce.
View Article and Find Full Text PDFCalcium-Binding Proteins in the Autistic Brain-Potential Links to Symptom Development.
Int J Dev Neurosci
February 2025
Faculty of Health Sciences, Department of Biomedical Sciences, State University of Rio Grande do Norte, Mossoró, Rio Grande do Norte, Brazil.
Autism spectrum disorder (ASD) is a complex challenge, influenced by genetic and environmental factors. This review focuses on the proteins calbindin (CB), calretinin (CR) and parvalbumin (PV) in the context of ASD, exploring their clinical correlations and providing a deeper understanding of the spectrum. In addition, we seek to understand the role of these proteins in GABAergic regulation and their implication in the pathophysiology of ASD.
View Article and Find Full Text PDFQ241R mutation of Braf causes neurological abnormalities in a mouse model of cardio-facio-cutaneous syndrome, independent of developmental malformations.
Hum Mol Genet
January 2025
Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, 3-39-22 Showa-machi, Maebashi, Gunma 371-8514, Japan.
Constitutively active mutants of BRAF cause cardio-facio-cutaneous (CFC) syndrome, characterized by growth and developmental defects, cardiac malformations, facial features, cutaneous manifestations, and mental retardation. An animal model of human CFC syndrome, the systemic BrafQ241R/+ mutant mouse, has been reported to exhibit multiple CFC syndrome-like phenotypes. In this study, we analyzed the effects of Braf mutations on neural function, separately from their effects on developmental processes.
View Article and Find Full Text PDFWant 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!