Our previous study showed the intrinsic ability of descending noradrenergic neurons projecting from the locus coeruleus to the spinal dorsal horn (SDH) to suppress itch-related behaviors. Noradrenaline and α-adrenaline receptor (α-AR) agonist increase inhibitory synaptic inputs onto SDH interneurons expressing gastrin-releasing peptide receptors, which are essential for itch transmission. However, the contribution of α-ARs expressed in SDH inhibitory interneurons to itch-related behavior remains to be determined. In this study, RNAscope in situ hybridization revealed that Adra1a mRNA is expressed in SDH inhibitory interneurons that are positive for Slc32a1 mRNA (known as vesicular GABA transporter). Mice with conditional knock-out of α-ARs in inhibitory interneurons (Vgat-Cre;Adra1a mice) exhibited an increase in scratching behavior when induced by an intradermal injection of chloroquine, but not compound 48/80, which are known as models of histamine-independent and dependent itch, respectively. Furthermore, knockout of inhibitory neuronal α-ARs in the SDH using the CRISPR-Cas9 system also increased the scratching behavior elicited by chloroquine but not compound 48/80. Our findings demonstrated for the first time that α-ARs in SDH inhibitory interneurons contribute to the regulation of itch signaling with preference for histamine-independent itch.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962300 | PMC |
| http://dx.doi.org/10.1186/s13041-021-00768-9 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Angiotensin IV Receptors in the Rat Prefrontal Cortex: Neuronal Expression and NMDA Inhibition.
Biomedicines
December 2024
Department of Oral Biology, Semmelweis University, H-1089 Budapest, Hungary.
Background: N-methyl-D-aspartate type glutamate receptors (NMDARs) are fundamental to neuronal physiology and pathophysiology. The prefrontal cortex (PFC), a key region for cognitive function, is heavily implicated in neuropsychiatric disorders, positioning the modulation of its glutamatergic neurotransmission as a promising therapeutic target. Our recently published findings indicate that AT receptor activation enhances NMDAR activity in layer V pyramidal neurons of the rat PFC.
View Article and Find Full Text PDFKetamine administration during adolescence impairs synaptic integration and inhibitory synaptic transmission in the adult dentate gyrus.
Prog Neurobiol
January 2025
Centro de Neurobiología y Fisiopatología Integrativa (CENFI), Instituto de Fisiología, Universidad de Valparaíso, Valparaíso 2340000, Chile; Millennium Nucleus of Neuroepigenetics and Plasticity (EpiNeuro), Santiago, Chile. Electronic address:
Ketamine administration during adolescence affects cognitive performance; however, its long-term impact on synaptic function and neuronal integration in the hippocampus a brain region critical for cognition remains unclear. Using functional and molecular analyses, we found that chronic ketamine administration during adolescence exerts long-term effects on synaptic integration, expanding the temporal window in an input-specific manner affecting the inner molecular layer but not the medial perforant path inputs in the adult mouse dorsal hippocampal dentate gyrus. Ketamine also alters the excitatory/inhibitory balance by reducing the efficacy of inhibitory inputs likely due to a reduction in parvalbumin-positive interneurons number and function.
View Article and Find Full Text PDFCell-type-specific networks during hippocampal seizures at the micro- and macroscale.
Brain
January 2025
Department of Neurology, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou 510120, China.
Epilepsy is a network disorder, involving neural circuits at both the micro- and macroscale. While local excitatory-inhibitory imbalances are recognized as a hallmark at the microscale, the dynamic role of distinct neuron types during seizures remain poorly understood. At the macroscale, interactions between key nodes within the epileptic network, such as the central median thalamic nucleus (CMT), are critical to the, hippocampal epileptic process.
View Article and Find Full Text PDFNeonatal but not Juvenile Gene Therapy Reduces Seizures and Prolongs Lifespan in SCN1B-Dravet Syndrome Mice.
J Clin Invest
January 2025
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, United States of America.
Dravet syndrome (DS) is a developmental and epileptic encephalopathy (DEE) that begins in the first year of life. While most cases of DS are caused by variants in SCN1A, variants in SCN1B, encoding voltage-gated sodium channel β1 subunits, are also linked to DS or to the more severe early infantile DEE. Both disorders fall under the OMIM term DEE52.
View Article and Find Full Text PDFThe role of neuroinflammation in PV interneuron impairments in brain networks; implications for cognitive disorders.
Rev Neurosci
January 2025
Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Children's Medical Center Hospital, Dr. Qarib St, Keshavarz Blvd, Tehran 14194, Iran.
Fast spiking parvalbumin (PV) interneuron is an inhibitory gamma-aminobutyric acid (GABA)ergic interneuron diffused in different brain networks, including the cortex and hippocampus. As a key component of brain networks, PV interneurons collaborate in fundamental brain functions such as learning and memory by regulating excitation and inhibition (E/I) balance and generating gamma oscillations. The unique characteristics of PV interneurons, like their high metabolic demands and long branching axons, make them too vulnerable to stressors.
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!