Biology subjects

Curti, S.

Publications and source records attributed to Curti, S..

4 recordsLinked to original sources

bioRxiv2025

Coincidence detection supported by electrical synapses is shaped by the D-type K+ current

Electrical synapses mediated by gap junctions are widespread in the mammalian brain, playing essential roles in neural circuit function. Beyond their role synchronizing neuronal activity, they also support complex computations such as coincidence detection--a circuit mechanism in which differences in input timing are encoded by the firing rates of coupled neurons, enabling preferential responses to synchronous over temporally dispersed inputs. Electrical coupling allows each neuron to act as a current sink for its partner during independent depolarizations, thereby reducing excitability. In contrast, synchronous inputs across the network minimize voltage differences through gap junctions, reducing current shunting and increasing spiking probability. However, the contribution of intrinsic neuronal properties to coincidence detection remains poorly understood. Here, we investigated this issue in the Mesencephalic Trigeminal (MesV) Nucleus of mice, a structure composed of somatically-coupled neurons. Using whole-cell recordings and pharmacological tools, we examined the role of the D-type K+ current (ID), finding that it critically shapes both the intrinsic electrophysiological properties of MesV neurons and the dynamics of electrical synaptic transmission. Its fast activation kinetics and subthreshold voltage range of activation make ID a key determinant of transmission strength and timing. Furthermore, the ID, likely mediated by Kv1 subunits, is expressed at the soma and the axon initial segment. Finally, we characterized two key parameters of coincidence detection--precision (time window for effective input summation) and gain (differential response to coincident versus dispersed inputs)--finding that ID enhances precision by accelerating membrane repolarization and reduces the gain by limiting neuronal excitability. SUMMARYElectrical synapses enable neural circuits to perform as coincidence detectors, that is, to preferentially respond to simultaneous inputs. The temporal precision of this operation is critically determined by voltage-dependent conductances of the soma and proximal axon.

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↗

bioRxiv2023

D-type K+ current controls the function of electrically coupled neurons in a species-specific fashion

Electrical synapses supported by gap junctions, are known to form networks of electrically coupled neurons in many regions of the mammalian brain, where they play relevant functional roles. Yet, how electrical coupling support sophisticated network operations, and the contribution of the intrinsic electrophysiological properties of neurons to these operations, remains incompletely understood. Here, comparative analysis of electrically coupled mesencephalic trigeminal (MesV) neurons, uncovered remarkable difference in the operation of these networks in highly related species. While spiking of MesV neurons might support the recruitment of coupled cells in rats, this rarely occurs in mice. Using whole-cell recordings, we determined that the higher efficacy in postsynaptic recruitment in rats MesV neurons does not result from coupling strength of larger magnitude, but instead from the higher excitability of coupled neurons. Consistently, MesV neurons from rats present a lower threshold current for activation, more hyperpolarized firing level as well as a higher ability to generate repetitive discharges, in comparison to their counterparts from mice. This difference in neuronal excitability results from a significantly higher magnitude of the D-type K+ current (ID) in MesV neurons from mice, indicating that the expression level of this current gates the recruitment of postsynaptic coupled neurons. Since MesV neurons are primary afferents critically involved in the organization of orofacial behaviors, such mechanism might support lateral excitation, by which activation of single neurons at the periphery can spread to coupled partners. Thus, by amplifying sensory inputs, lateral excitation may significantly contribute to information processing and organization of motor outputs.

neuroscience↗

bioRxiv2021

Maturation signatures of conventional dendritic cells in COVID-19 reflect direct viral sensing

Growing evidence suggests that conventional dendritic cells (cDCs) undergo aberrant maturation in COVID-19 and this negatively affects T cell activation. The presence of functional effector T cells in mild patients and dysfunctional T cells in severely ill patients suggests that adequate T cell responses are needed to limit disease severity. Therefore, understanding how cDCs cope with SARS-CoV-2 infections can help elucidate the mechanism of generation of protective immune responses. Here, we report that cDC2 subtypes exhibit similar infection-induced gene signatures with the up-regulation of interferon-stimulated genes and IL-6 signaling pathways. The main difference observed between DC2s and DC3s is the up-regulation of anti-apoptotic genes in DC3s, which explains their accumulation during infection. Furthermore, comparing cDCs between severe and mild patients, we find in the former a profound down-regulation of genes encoding molecules involved in antigen presentation, such as major histocompatibility complex class II (MHCII) molecules, {beta}2 microglobulin, TAP and costimulatory proteins, while an opposite trend is observed for proinflammatory molecules, such as complement and coagulation factors. Therefore, as the severity of the disease increases, cDC2s enhance their inflammatory properties and lose their main function, which is the antigen presentation capacity. In vitro, direct exposure of cDC2s to the virus recapitulates the type of activation observed in vivo. Our findings provide evidence that SARS-CoV-2 can interact directly with cDC2s and, by inducing the down-regulation of crucial molecules required for T cell activation, implements an efficient immune escape mechanism that correlates with disease severity.

immunology↗