Biology subjects

Trigo, F. F.

Publications and source records attributed to Trigo, F. F..

4 recordsLinked to original sources

bioRxiv2026

Connexins are essential for the contribution of latent progenitors to self-repair after spinal cord injury

Gap junctions are important regulators of the biology of neural stem cells. Both in vertebrates with regenerative abilities and neonatal rodents, ependymal cells communicate via connexin (Cx) 43 and Cx26. Gap junction coupling and Cx26 are down-regulated as the ependyma becomes quiescent in adulthood, but injury overrules this developmental down-regulation suggesting a role for Cx signalling in the reactivation of ependymal cells. Here, we aim to explore the role of Cx26 and Cx43 in the response of ependymal cells to injury. We find that Cx26 is critical for the proliferative response to injury and thereby scar formation. Cx43 plays a key role in the communication between ependymal cells of Ca2+ signals induced by activation of P2X7 receptors that trigger downstream events. Our data show that Cxs are relevant targets to manipulate the ependymal stem cell niche to achieve a better self-repair after spinal cord injury.

neuroscience↗

bioRxiv2025

PH sensitivity of cerebrospinal fluid-contacting neurons involves the modulation of phasic and tonic currents mediated by PKD2L1 channels located in the apical process.

Cerebrospinal fluid contacting neurons (CSFcNs) are GABAergic cells that surround the central canal (cc) of the spinal cord. Their soma is located sub-ependymally and they have a dendritic-like process that ends as a bulb (the so-called "apical process"; ApPr) inside the cc. It remains unclear how this unique anatomical organization, with the soma and the ApPr located in different extracellular environments, relates to their function as a multimodal sensor of cerebrospinal fluid (CSF) composition. One of the main physiological features of CSFcNs is a prominent spontaneous electrical activity mediated by PKD2L1 channels, a non-selective cation channel of the TRP family. PKD2L1 channels have a high single-channel conductance (around 200 pS) and can be modulated by protons and mechanical forces. In this work we investigate PKD2L1 channel sensitivity to pH and its effects on CSFcNs excitability. We demonstrate that PKD2L1 spontaneous activity generates not only phasic inward currents, but also a sustained current, both of which are modulated bidirectionally by pH with a high sensitivity around physiological values. By combining electrophysiology (direct recordings from intact and isolated ApPrs) with optical methods (laser-photolysis of protons) we further show that functional PKD2L1 channels are specifically localized in the ApPr. The spatial segregation of PKD2L1 channels, along with their biophysical properties (high single-channel conductance and pH sensitivity) and the ApPrs unique membrane properties (very high input resistance) renders CSFcN excitability exquisitely sensitive to PKD2L1 modulation. Altogether, our findings illustrate how the ApPrs properties are finely tuned to support its sensory role.

neuroscience↗

bioRxiv2025

Functional interaction of electrical coupling and H-current and its putative impact on inhibitory transmission

The flow of information within neural circuits depends on the communication between neurons, primarily taking place at chemical and electrical synapses. The coexistence of these two modalities of synaptic transmission and their dynamical interaction with voltage-gated membrane conductances enables a rich repertoire of complex functional operations. One such operation, coincidence detection, allows electrically coupled neurons to respond more strongly to simultaneous synaptic inputs than to temporally dispersed ones. Using the mesencephalic trigeminal (MesV) nucleus--a structure composed of large, somatically coupled neurons--as an experimental model, we first demonstrate that electrical coupling strength in the hyperpolarized voltage range is highly time-dependent due to the involvement of the IH current. We then show how this property influences the coincidence detection of hyperpolarizing signals. Specifically, simultaneous hyperpolarizing inputs induce larger membrane potential changes, resulting in stronger IH current activation. This, in turn, shortens the temporal window for coincidence detection. We propose that this phenomenon may be crucial for networks dynamics in circuits of electrically coupled neurons that receive inhibitory synaptic inputs and express the IH current. In particular, molecular layer interneurons (MLIs) of the cerebellar cortex provide an ideal model for studying coincidence detection of inhibitory synaptic inputs, and how this operation is shaped by the voltage-dependent conductances like the IH current, potentially impacting on motor coordination and learning.

neuroscience↗

bioRxiv2022

Analogue signaling of somato-dendritic synaptic activity to axon enhances GABA release in young cerebellar molecular layer interneurons

Axons are equipped with the digital signaling capacity by which they generate and faithfully propagate action potentials (APs), and also with the analogue signaling capacity by which subthreshold activity in dendrites and soma is transmitted down the axon. Despite intense work, the extent and physiological role for subthreshold synaptic activity reaching the axonal boutons has remained elusive because of the technical limitation to record from them. To address this issue, we made simultaneous patch-clamp recordings from the axonal varicosities of cerebellar GABAergic interneurons together with their parent soma or postsynaptic target cells in young rat slices and/or primary cultures. Our tour-de-force direct functional dissection indicates that the somatodendritic spontaneous EPSPs are transmitted down the axon for significant distances, depolarizing presynaptic boutons. These analogously transmitted EPSPs augment presynaptic Ca++ influx upon arrival of an immediately following AP through a mechanism that involves a voltage-dependent priming of the Ca++ channels, leading to an increase in GABA release, without any modification in the axonal AP waveform or residual Ca++. Our work highlights the role of the axon in synaptic integration.

neuroscience↗