Biology subjects

Jehasse, K.

Publications and source records attributed to Jehasse, K..

4 recordsLinked to original sources

bioRxiv2025

A fast and tiny current as common generator of slow regular pacemaking in brain and heart

Slow pacemaking is a key physiological process in specific excitable cells, yet its underlying mechanism remains debated. Here we identify a conserved, voltage-dependent pacemaker current that is essential for slow, regular firing in both midbrain dopaminergic neurons and sinoatrial node myocytes. Conductance-based models incorporating this current reproduce stable pacemaking, requiring a fast-activating, small-amplitude current. This is further confirmed by dynamic-clamp experiments in dopaminergic neurons. Replacing the pacemaker current in a model with a voltage-independent conductance such as the non-selective sodium leak channels fails to sustain slow rhythmicity, highlighting the necessity for an adequate voltage dependence. Our results suggest a novel and shared biophysical mechanism for slow pacemaking in neuronal and cardiac systems.

physiology↗

bioRxiv2024

Co-agonist glycine controls the occurrence of bursts by activating extrasynaptic NMDARs in nigral dopamine neurons

NMDA receptor activation in pars compacta substantia nigra dopamine neurons is central to the generation of bursting activity, a key signal temporally associated to movement initiation. The site of the NMDAR pool (synaptic and/or extrasynaptic) as well as the identity of the co-agonist involved in the ignition of this phasic activity remains unknown. Using ex vivo electrophysiological recordings, we demonstrate that NMDARs located outside synapses are preponderant for this firing. This pool of receptors is recruited during intense synaptic activity via spillover of glutamate and require the binding of NMDAR co-agonist glycine for their full activation. Synaptic NMDARs are not directly involved in bursting and are activated by D-serine, a distinct co-agonist. Location dependency of NMDARs and co-agonist underlying burst generation may serve as a guideline in understanding the physiological role of dopamine neurons in health and disease. TeaserExtrasynaptic NMDARs recruited by spillover and glycine allow the generation of bursts in dopamine neurons.

neuroscience↗

bioRxiv2022

Immediate reuse of patch-clamp pipettes with ultrasonic cleaning

The patch-clamp technique has revolutionized neurophysiology by allowing to study single neuronal excitability, synaptic connectivity, morphology, and the transcriptomic profile. However, the throughput in recordings is limited because of the manual replacement of patch-pipettes after each attempt which are often also unsuccessful. This has been overcome by automated cleaning the tips in detergent solutions, allowing to reuse the pipette for further recordings. Here, we developed a novel method of automated cleaning by sonicating the tips within the bath solution wherein the cells are placed, reducing the risk of contaminating the bath solution or internal solution of the recording pipette by any detergent and avoiding the necessity of a separate chamber for cleaning. We showed that the patch-pipettes can be used consecutively at least 10 times and that the cleaning process does not negatively impact neither the brain slices nor other patched neurons. This method, combined with automated patch-clamp, highly improves the throughput for single and especially multiple recordings.

neuroscience↗

bioRxiv2020

An unconventional conductance is required for pacemaking of nigral dopamine neurons

Although several ionic mechanisms are known to control rate and regularity of the pacemaker in dopamine (DA) neurons from the substantia nigra pars compacta (SNc), a conductance essential for pacing has yet to be defined. Here we provide pharmacological evidence that pacemaking of SNc DA neurons is enabled by an unconventional conductance. We found that 1-(2,4-xylyl)guanidine (XG), an established blocker of gating pore currents in mutant voltage gated sodium channels, selectively stops pacemaking of DA SNc neurons and is without effect on the main pore of their voltage-gated channels. We isolated a voltage-dependent, non-inactivating XG-sensitive current of 20-25 pA which operates in the relevant subthreshold range and is carried by both Na+ and Cl- ions. While the molecular identity of this conductance remains to be determined, we show that this XG-sensitive current is crucial to sustain pacemaking in these neurons.

neuroscience↗