In the presence of 4-aminopyridine (4-AP) and excitatory amino acid receptor blockers, GABAergic networks in the neocortex give rise to large spontaneous GABA-mediated depolarizations. We used voltage-sensitive dye techniques to explore the network properties of depolarizing GABA responses. Voltage-sensitive dye signals demonstrated that the superficial layers support the propagation of depolarizing GABA responses, with only minimal signals detected in deeper cortical layers. GABA responses propagated at a speed of 2.7 +/- 0.2 mm/s, a rate intermediate to fast synaptic transmission and spreading depression. Changes in the extracellular potassium concentration altered the propagation speed of the depolarizing GABA response. Taken together, these data support a role for both direct synaptic action of GABA at GABA(A) receptors and nonsynaptic mechanisms in the generation and propagation of depolarizing GABA responses.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.devbrainres.2005.03.008 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Infantile Spasms in Pediatric Down Syndrome: Potential Mechanisms Driving Therapeutic Considerations.
Children (Basel)
December 2024
Division of Pediatric Neurology, Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Infantile spasms are common in Down Syndrome (DS), but the mechanisms by which DS predisposes to this devastating epilepsy syndrome are unclear. In general, neuronal excitability and therefore seizure predisposition results from an imbalance of excitation over inhibition in neurons and neural networks of the brain. Animal models provide clues to mechanisms and thereby provide potential therapeutic approaches.
View Article and Find Full Text PDFEffects of ketamine and propofol on muscarinic plateau potentials in rat neocortical pyramidal cells.
PLoS One
January 2025
Department of Molecular Medicine, Brain Signalling Laboratory, Institute of Basic Medical Sciences, Section for Physiology, University of Oslo, Oslo, Norway.
Propofol and ketamine are widely used general anaesthetics, but have different effects on consciousness: propofol gives a deeply unconscious state, with little or no dream reports, whereas vivid dreams are often reported after ketamine anaesthesia. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist, while propofol is a γ-aminobutyric-acid (GABAA) receptor positive allosteric modulator, but these mechanisms do not fully explain how these drugs alter consciousness. Most previous in vitro studies of cellular mechanisms of anaesthetics have used brain slices or neurons in a nearly "comatose" state, because no "arousing" neuromodulators were added.
View Article and Find Full Text PDFDevelopment of KCC2 therapeutics to treat neurological disorders.
Front Mol Neurosci
December 2024
Axonis Therapeutics Inc., Boston, MA, United States.
KCC2 is CNS neuron-specific chloride extruder, essential for the establishment and maintenance of the transmembrane chloride gradient, thereby enabling synaptic inhibition within the CNS. Herein, we highlight KCC2 hypofunction as a fundamental and conserved pathology contributing to neuronal circuit excitation/inhibition (E/I) imbalances that underly epilepsies, chronic pain, neuro-developmental/-traumatic/-degenerative/-psychiatric disorders. Indeed, downstream of both acquired and genetic factors, multiple pathologies (e.
View Article and Find Full Text PDFPharmacological blocking of spinal GABA receptors in monkeys reduces sensory transmission to the spinal cord, thalamus, and cortex.
Cell Rep
December 2024
Rehab Neural Engineering Labs, University of Pittsburgh, Pittsburgh, PA, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; Center for Neural Basis of Cognition, Pittsburgh, PA, USA; Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA; Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address:
A century of research established that GABA inhibits proprioceptive inputs presynaptically to sculpt spinal neural inputs into skilled motor output. Recent results in mice challenged this theory by showing that GABA can also facilitate action potential conduction in proprioceptive afferents. Here, we tackle this controversy in monkeys, the most human-relevant animal model, and show that GABA receptors (GABARs) indeed facilitate sensory inputs to spinal motoneurons and interneurons and that this mechanism also influences sensory transmission to supraspinal centers.
View Article and Find Full Text PDFA Comprehensive Functional Investigation of the Human Translocator Protein 18 kDa (TSPO) in a Novel Human Neuronal Cell Knockout Model.
Int J Mol Sci
November 2024
Department of Psychiatry and Psychotherapy, University of Regensburg, 93053 Regensburg, Germany.
The translocator protein 18 kDa (TSPO) is a multifunctional outer mitochondrial membrane protein associated with various aspects of mitochondrial physiology and multiple roles in health and disease. Here, we aimed to analyse the role of TSPO in the regulation of mitochondrial and cellular functions in a human neuronal cell model. We used the CRISPR/Cas9 technology and generated TSPO knockout (KO) and control (CTRL) variants of human-induced pluripotent stem cells (hiPSCs).
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!