Biology subjects

Covelo, A.

Publications and source records attributed to Covelo, A..

3 recordsLinked to original sources

bioRxiv2025

Identification of TREK channels in mouse intracardiac ganglion neurons

The intracardiac nervous system is a complex neural network formed by a diffuse plexus, the so-called intracardiac ganglion (ICG). These ganglia locally innervate and control heart function, but little is known about how ICG neuronal activity is regulated. While various ionic currents have been characterized in cardiac tissue, the expression and role of TREK channels in ICG neurons remain unexplored. TWIK-related K+ (TREK) channels, members of the two-pore domain potassium channel family, are essential regulators of neuronal membrane resting potential and excitability, with recognized neuroprotective functions. In this study, we have characterized different ionic currents present in mouse ICG neurons, including tetrodotoxin-sensitive Na currents, delayed K+ rectifiers, Ca+2-dependent K currents and A, H and M currents. Notably, we provide the first evidence of functional TREK channel expression in these neurons. Our findings suggest that TREK channels contribute to excitability control and cellular homeostasis in ICG neurons, underscoring their potential as therapeutic targets for cardiac disorders. KEY POINTS- This study provides the first evidence of functional TREK channel expression in ICG neurons. - Comprehensive profiling of ionic currents shaping excitability in ICG neurons. - Neuroprotective TREK channels might emerge as potential therapeutic targets for cardiac disorders.

neuroscience↗

bioRxiv2022

Cannabinoids regulate an insula circuit controlling water intake

The insular cortex, or insula, is a large brain region involved in the detection of thirst and the control of water intake. However our understanding of the topographical, circuit and molecular mechanisms the controlling water intake within the insula remains parcellated. We found that type-1 cannabinoid receptors (CB1) within the insular cortex participate to the regulation of water intake, and deconstructed circuit mechanisms of this control. Topographically, we revealed that the activity of excitatory neurons in both anterior (aIC) and posterior (pIC) insula increases in response to water intake, yet removal of CB1 receptors only in the pIC decreases water intake. Interestingly, we found that CB1 receptors are highly expressed in insula projections to the basolateral amygdala (BLA), while undetectable in the neighboring central part of the amygdala. Thus, we imaged the neurons of the anterior or posterior insula targeting the BLA (aIC-BLA and pIC-BLA), and found they oppositely respond to water intake, respectively decreasing and increasing their activity upon water drinking. Consistently, chemogenetic activation of pIC-BLA neurons decreased water intake. Finally, we uncovered CB1-dependent short term synaptic plasticity (depolarization-induced suppression of excitation, DSE) selectively in pIC-BLA, compared to aIC-BLA synapses. Altogether, our results support a model where CB1 signaling in the pIC-BLA pathway exerts a positive control on water intake.

neuroscience↗

bioRxiv2020

Astroglial calcium transfer from endoplasmic reticulum to mitochondria determines synaptic integration

Intracellular calcium signaling underlies the astroglial control of synaptic transmission and plasticity. Mitochondria-endoplasmic reticulum contacts (MERCs) are key determinants of calcium dynamics, but their functional impact on astroglial regulation of brain information processing is currently unexplored. We found that the activation of astrocyte mitochondrial-associated CB1 receptors (mtCB1) determines MERCs-dependent intracellular calcium signaling and synaptic integration. The stimulation of mtCB1 receptors promotes calcium transfer from the endoplasmic reticulum to mitochondria through specific mechanisms regulating the activity of the mitochondrial calcium uniporter (MCU) channel. Physiologically, mtCB1-dependent mitochondrial calcium uptake determines the precise dynamics of cytosolic calcium events in astrocytes upon endocannabinoid mobilization. Accordingly, electrophysiological recordings in hippocampal slices showed that genetic exclusion of mtCB1 receptors or specific astroglial MCU inhibition blocks lateral synaptic potentiation, a key example of astrocyte-dependent integration of distant synapses activity. Altogether, these data reveal an unforeseen link between astroglial MERCs and the regulation of brain network functions.

neuroscience↗