Topic: whole-cell patch-clamp

To position his feet correctly on the wire, tightrope walker needs precise sensory feedback. This skilled motor behaviour requires the rapid integration of external sensory input to achieve accuracy in foot placement while keeping the balance. Neurones in contact with the cerebrospinal fluid (CSF-cNs), localized around the medullo-spinal central canal in all vertebrates, are GABAergic and selectively express PKD2L1 channel (Polycystin Kidney Disease 2-like1), a member of TRP superfamily, with chemo/mechanosensitive properties. In zebrafish, CSF-cNs respond to spinal cord bending and modulat

The claustrum is a telencephalic nucleus that likely dates back to the common ancestor of amniotes. It is one of the most highly connected regions of the mammalian brain, with massive reciprocal projections to the cerebral cortex and certain subcortical regions. The function of this “brain hub” still remains elusive but several hypotheses emerged, such as the claustrum being crucial for some attentional processes and cognitive control, but also for the modulation of cortical slow-wave synchronization during sleep and quiet wakefulness (Narikiyo, Nat.Neurosci 2020; Marriott, Cell Rep. 2024). Us

Autism Spectrum Disorder (ASD) is characterized mainly by social and sensory-motor abnormal and repetitive behavior patterns. Over hundreds of genes and thousands of genetic variants were reported to be highly penetrant and causative of ASD. Many of these mutations cause comorbidities such as epilepsy and intellectual disabilities (ID). In this study, we measured cortical neurons derived from induced pluripotent stem cells (iPSCs) of patients with four mutations in the genes GRIN2B, SHANK3, UBTF, as well as chromosomal duplication in the 7q11.23 region and compared them to neurons derived from

AIMS:Investigate whether the endoplasmic reticulum (ER) quality control machinery verifies the structure of ligand-binding domains (LBDs) of NMDARs or controls the functionality of NMDARs.METHODS:HEK293 cells were used to express wild-type (WT) or mutation forms of GluN1/GluN2A and GluN1/GluN2B receptors. Surface expressions were observed using fluorescence confocal microscopy. Electrophysiological properties of NMDARs were assessed via the whole-cell patch-clamp technique.RESULTS:Using alanine substitutions combined with microscopy and electrophysiology, we found that surface expression of Gl

In the retina, multiple processing steps contribute to the neuronal signals sent to higher visual centers. Retinal ganglion cells (RGCs) are the final output neurons in the retinal pathway; their output is thought to be mainly determined by presynaptic inputs; however, recent evidence suggests that the biophysical properties of RGCs such as the axon initial segment (AIS) also play an important part in signal modulation.Whole-cell patch-clamp experiments were performed to measure the spiking responses of ON-alpha sustained (ON-αs), OFF-alpha sustained (OFF-αs), and OFF-alpha transient (OFF-αt)

Recent evidence suggests an anti-hypertensive effect for the pineal neurohormone melatonin (MT) as it promotes vasorelaxation through concentration-, receptor-, and vessel-dependent mechanisms. Interestingly, Kv7.4 activation results to be a downstream effect of several vasorelaxants that activate the cAMP signalling cascade. Furthermore, positive modulation of Kv7.4 also appears to be the mechanism by which hydrogen sulphide (H2S) mediates vasorelaxation. In fact, the H2S-donor sodium hydrogen sulphide (NaHS) promoted endothelial-independent relaxations of rat aortic rings by facilitating Kv7

Neurons derived from induced pluripotent stem cells (h-iPSC-Ns) provide an invaluable model for studying the physiological aspects of neuronal development and diseases. However, multiple studies have also demonstrated that h-iPSC-Ns exhibit a high degree of functional and epigenetic diversity. Due to the imprecise characterization and significant variation among the currently available maturation protocols, it is essential to establish a set of criteria to standardize models and accurately characterize and define the developmental properties of neurons derived from iPSCs. In this study, we con

Kv7.2 and Kv7.3 are voltage-gated potassium channels subunits mainly expressed in neurons where they underlie the M-current (IKM), a sub-threshold K+ current controlling action potentials generation and frequency. The Kv7.2/7.3 channel opener retigabine is an antiseizures drug used until 2017 when it was withdrawn from the market for safety reasons. Since then, no Kv7 activator is currently available for clinical use. We used a drug repurposing strategy to identify novel Kv7.2/3 activators. A library of 5600 compounds, mostly represented by clinically-approved drugs, was screened in CHO cells

Excitotoxicity is a central mechanism in the pathogenesis of different, currently incurable, neurodegenerative diseases. One treatment targeting excitotoxicity is Riluzole (Rilutek®), a drug capable of reducing glutamate release. Currently, Riluzole is available for patients with amyotrophic lateral sclerosis (ALS) to delay the progression of the disease. However, its efficacy diminishes in advanced stages of the pathology.The aim of this study has been to characterize the effect of a novel Riluzole-derived compound (VA945) as a potential neuroprotective drug, aiming at identify a more efficie

Short-term plasticity (STP) is the neuronal substrate for modification of the efficiency of synaptic transmission in the timescale of milliseconds to seconds. STP renders synapses the ability to process and integrate inputs which in-turn controls information flow and processing in networks. Our work explored the diversity in STP of hippocampal CA1 synapses and the summation of multiple inputs during STP in a CA1 neuron with balanced excitation and inhibition. We performed invitro experiments on the CA3-CA1 network in acute hippocampal slices from mice expressing channelrhodopsin specifically i