Approach for Electrophysiological Studies of Spinal Lamina X Neurons.

Despite playing diverse physiological roles, the area surrounding the central canal, lamina X, remains one of the least studied spinal cord regions. Technical challenges and limitations of the commonly used experimental approaches are the main difficulties that hamper lamina X research. In the current protocol, we describe a reliable method for functional investigation of lamina X neurons that requires neither time-consuming slicing nor sophisticated in vivo experiments.

Nerve Preparation and Recordings for Pharmacological Tests of Sensory and Nociceptive Fiber Conduction Ex Vivo.

Measuring signal propagation through nerves is a classical electrophysiological technique established decades ago to evaluate sensory and motor functions in the nervous system. The whole-nerve preparation provides a valuable model to investigate nerve function ex vivo; however, it requires specific knowledge to ensure successful and stable measurements. Although the methodology for sciatic nerve recordings has long existed, a method for reliable and long-lasting recordings from myelinated and non-myelinated (nociceptive) fibers still needs to be adapted for pharmacological testing.

Neuropathic pain changes the output of rat lamina I spino-parabrachial neurons.

• Spared nerve injury (SNI) altered the action potential (AP) output of lamina I spino-parabrachial neurons (SPNs) without affecting their resting potential or membrane resistance. • In one-third of SPNs, high-threshold dorsal root stimulation elicited persistent AP firing which was never observed in cells from naïve animals. • 38% of SPNs from SNI rats showed spontaneous persistent AP firing.

Elucidating afferent-driven presynaptic inhibition of primary afferent input to spinal laminae I and X.

Although spinal processing of sensory information greatly relies on afferent-driven (AD) presynaptic inhibition (PI), our knowledge about how it shapes peripheral input to different types of nociceptive neurons remains insufficient. Here we examined the AD-PI of primary afferent input to spinal neurons in the marginal layer, lamina I, and the layer surrounding the central canal, lamina X; two nociceptive-processing regions with similar patterns of direct supply by Aδ- and C-afferents. Unmyelinated C-fibers were selectively activated by electrical stimuli of negative polarity that induced an anodal block of myelinated Aβ/δ-fibers.

A gain-of-function GRIA2 variant associated with neurodevelopmental delay and seizures: Functional characterization and targeted treatment.

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors (AMPARs) are ligand-gated cationic channels formed from combinations of GluA1-4 subunits. Pathogenic variants of GRIA1-4 have been described in patients with developmental delay, intellectual disability, autism spectrum disorder, and seizures, with GRIA2 variants typically causing AMPAR loss of function. Here, we identify a novel, heterozygous de novo pathogenic missense mutation in GRIA2 (c.