Biology subjects

Debanne, D.

Publications and source records attributed to Debanne, D..

15 recordsLinked to original sources

bioRxiv2026

Gamma-frequency firing persistently enhances intrinsic excitability in retinal ganglion cells

Experience-dependent plasticity is usually attributed to synaptic changes, but neuronal output also depends on changes in intrinsic excitability. Whether intrinsic excitability is persistently modified at the retinal output stage is unknown. Using whole-cell recordings from retinal ganglion cells (RGCs) of juvenile rats, we found that 40-Hz firing produced sustained potentiation of intrinsic excitability in low-input-resistance A-type RGCs and rapid potentiation of intrinsic excitability in high-input-resistance B-type RGCs. In A-type bursting RGCs, long-term potentiation of intrinsic excitability (LTP-IE) required Cav1 calcium channels for its induction. LTP-IE was associated with hyperpolarization of spike threshold and reduction of spike time jitter, due to reduced Kv1 potassium-family channel function. Potentiation also increased the probability that visually-evoked synaptic events triggered action potentials. Patterned firing therefore persistently reconfigures RGC input-output transformation through the Cav1-dependent regulation of Kv1 channels, revealing intrinsic plasticity at the retinal output stage.

neuroscience↗

bioRxiv2026

Homeostatic regulation of intrinsic neuronal excitability in visual thalamic relay cells induced by brief monocular deprivation

Homeostatic plasticity of intrinsic excitability (IE) in the visual system has been essentially shown at the cortical level but whether thalamic nuclei also express homeostatic plasticity of IE is unknown. We show here that 4 days of monocular deprivation (MD) at eye opening induces a homeostatic change in IE in dorsal lateral geniculate nucleus (dLGN) neurons. Neurons recorded in the dLGN region activated by the deprived eye are more excitable than neurons recorded in the dLGN region activated by the open eye. No significant changes were observed following 7 days of MD, however. Enhanced excitability in neurons from the deprived side after 4 days of MD was associated with a reduced Kv1-dependent LTP-IE, a smaller voltage ramp, and a reduced inter-spike interval, suggesting that Kv1 channels are down-regulated in deprived dLGN neurons. Furthermore, the ankyrin G signal of the axon initial segment was larger in deprived dLGN neurons compared with open ones, indicating that Nav1 channel number also undergoes homeostatic regulation, and Kv1.1 channel signals were lower in deprived neurons compared to open ones. In addition, electrical coupling was found to be strengthened in neurons displaying enhanced IE following either brief (4 days) or long (10 days) MD. These results suggest that homeostatic and Hebbian plasticity in the dLGN share common expression mechanisms involving the regulation of Kv1 channels, Nav1 channels and electrical coupling between relay neurons.

neuroscience↗

bioRxiv2026

Persistent enhancement of intrinsic neuronal excitability induced by transient divalent cation depletion

Fluctuations in external calcium concentration [Ca2+]e occur during the wake and sleep cycle and during intense neuronal activity. However, the incidence of these fluctuations on neuronal excitability is not precisely known. We show here that reducing divalent cation (Ca2+ and Mg2+) concentrations from 1.3/0.8 to 0.6/0.4 mM during 15-30 minutes induces long-term potentiation of intrinsic excitability (LTP-IE) in CA1 pyramidal neurons. LTP-IE induced by low divalent cations is associated with a hyperpolarization of the action potential threshold and constitutes a positive feed-back of brain activity. This plasticity requires Ca2+-sensing receptor (CaSR), IP3 receptor (IP3R) and calcium-calmodulin kinase II (CaMKII). In fact, LTP-IE was occluded in the presence of the calcilytic NPS-2143 and absent in CRISPR CaSR neurons. In addition, inhibiting IP3R with 2-APB and CaMKII with kin considerably reduced LTP-IE magnitude. LTP-IE and synaptic potentiation (LTP) induced by spike-timing-dependent plasticity (STDP) protocol were also found to depend on CaSR as they were totally absent in CRISPR CaSR neurons. Spontaneous excitatory synaptic activity was found to be reduced by [~]35% following LTP induced by STDP. Importantly, this drop of spontaneous activity was not observed in CRISPR CaSR neurons. Taken together, these results show that CaSR plays a critical role in LTP-IE induced by low [Ca2+]e and [Mg2+]e and as well as in LTP of synaptic transmission and intrinsic excitability induced by STDP.

neuroscience↗

bioRxiv2025

Divalent cation depletion enhances neuronal excitability through CaSR-dependent modulation of threshold channels

External calcium ([Ca{superscript 2}]{square}) and magnesium ([Mg{superscript 2}]{square}) concentrations fluctuate across physiological and pathological brain states. For example, [Ca{superscript 2}]{square} decreases during intense neuronal activity and epilepsy, whereas it rises during sleep. Similarly, [Mg{superscript 2}]{square} varies with the sleep/wake cycle and is reduced in epilepsy. Lowering either [Ca2+]e or [Mg2+]e increases intrinsic excitability and hyperpolarizes the action potential (AP) threshold, yet the underlying mechanisms remain unclear. Here, we confirm that reducing [Ca2+]e or [Mg2+]e enhances intrinsic excitability and hyperpolarizes the AP threshold of CA1 pyramidal neurons. Physiological reductions in [Mg{superscript 2}]{square} (0.8 [->] 0.4 mM) have minimal effect, whereas decreases from supraphysiological levels (2.0 [->] 0.4 mM) robustly increase excitability. Using pharmacology and CRISPR/Cas9 gene editing, we identify the calcium-sensing receptor (CaSR) as a key mediator of these effects. The calcilytic NPS-2143 mimics and largely occludes both the intrinsic excitability increase and the AP-threshold hyperpolarization, while genetic reduction of CaSR produces similar outcomes. We further show that AP-threshold hyperpolarization induced by low divalent cations involves both Kv1 and Nav1.2 channels. Together, these findings reveal CaSR as a critical link between external divalent cation levels and intrinsic neuronal excitability through the modulation of Kv1 and Nav channels.

neuroscience↗

bioRxiv2025

Somatostatin released by single O-LM interneurons slowly inhibits intrinsic neuronal excitability in a paracrine and autocrine manner

Somatostatin (SST) is a neuropeptide known to inhibit both neuronal excitability and excitatory synaptic transmission in principal neurons. While SST is expressed in some GABAergic interneurons such as Oriens-Lacunosum Moleculare (O-LM) cells, the precise conditions governing SST release remain poorly defined. We show here that, in the presence of GABAA receptor antagonist, single O-LM interneurons of CA1 are able to inhibit pyramidal neuron excitability when O-LM cells fire at frequencies above 20 Hz. This inhibition is suppressed by the SST receptor antagonist cyclo-SST and is absent when the O-LM interneuron is located more than 150 {micro}m from the pyramidal cell. Likewise, a single O-LM cell was also able to inhibit the intrinsic excitability of another O-LM cell, provided the two cells are in proximity. Exogeneous application of SST transiently inhibits excitatory synaptic transmission and intrinsic excitability in O-LM interneurons through SST1 and SST2, respectively. Notably, this transient inhibition became sustained when clathrin-dependent endocytosis of SST receptors was blocked. Blocking of SST receptors reduced NMDA receptor-mediated responses, prevented induction of both synaptic and intrinsic potentiation in pyramidal neurons and reduced the coherence of theta oscillations. These findings reveal that SST released by O-LM interneurons constitutes an additional inhibitory mechanism, modulating both synaptic excitation and intrinsic excitability beyond the transient inhibition mediated by GABA release.

neuroscience↗

bioRxiv2025

Unreliable homeostatic action potential broadening in cultured dissociated neurons

Homeostatic plasticity preserves neuronal activity against perturbations. Recently, somatic action potential broadening was proposed as a key homeostatic adaptation to chronic inactivity in neocortical neurons. Since action potential shape critically controls calcium entry and neuronal function, broadening provides an attractive homeostatic feedback mechanism to regulate activity. Here, we report that chronic inactivity induced by sodium channel block does not broaden action potentials in neocortical neurons under a wide range of conditions. In contrast, action potentials were broadened in CA3 neurons of organotypic hippocampal cultures by chronic sodium channel block and in hippocampal dissociated cultures by chronic synaptic block. Mechanistically, BK-type potassium channels were proposed to underly inactivity-induced action potential broadening. However, BK channels did not affect action potential duration in our recordings. Our results indicate that action potential broadening can occur in specific neurons and conditions but is not a general mechanism of homeostatic plasticity in cultured neurons.

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bioRxiv2023

Visual activity enhances neuronal excitability in thalamic relay neurons

The dorsal lateral geniculate nucleus (dLGN) has long been held to act as a basic relay for visual information travelling from the retina to cortical areas, but recent findings suggest a largely underestimated functional plasticity of dLGN neurons. However, the cellular mechanisms supporting this functional plasticity have not been yet explored. In particular, it remains to elucidate whether intrinsic neuronal excitability change upon visual stimuli. We show here that monocular deprivation for 10 days reduces the intrinsic excitability of dorsal LGN relay cells. Furthermore, dLGN neurons exhibit long-term potentiation of their intrinsic excitability (LTP-IE) when suprathreshold afferent retinal inputs are stimulated at 40 Hz or when spikes are induced with direct somatic current injection to reproduce patterns of retinal activity. LTP-IE is observed after eye opening and requires calcium influx mediated by L-type calcium channels. It involves activation of PKA and is expressed through the down-regulation of Kv1 potassium channels. In conclusion, our study provides the first evidence for intrinsic plasticity in dLGN relay cells, thus further pointing the role of thalamic neurons in activity-dependent visual plasticity and amblyopia.

neuroscience↗

bioRxiv2023

Rescue of normal excitability in LGI1-deficient epileptic neurons

Leucine-rich Glioma Inactivated 1 (LGI1) is a glycoprotein secreted by neurons, the deletion of which leads to Autosomal Dominant Lateral Temporal Lobe Epilepsy. Recently, we showed that LGI1 deficiency in a mouse model (KO-Lgi1) decreased Kv1.1 channel density at the axon initial segment (AIS) and at presynaptic terminals, thus enhancing both intrinsic excitability and glutamate release. However, the precise conditions for rescuing normal excitability in KO-Lgi1 neurons have still not been reported. Here we show that the selective expression of LGI1 in KO-Lgi1 neurons with the use of single-cell electroporation reduces intrinsic excitability, and restores both the Kv1.1 mediated D-type current and Kv1.1 immunostaining at the AIS. In addition, we show that the homeostatic shortening of the AIS length observed in KO-Lgi1 neurons is prevented in neurons electroporated with the Lgi1 gene. Furthermore, we reveal a spatial gradient of both intrinsic excitability and Kv1.1 immunostaining that is centred on the electroporated neuron. We conclude that expression of LGI1 restores normal excitability through the expression of functional Kv1 channels at the AIS.

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bioRxiv2022

Synaptic and intrinsic potentiation in O-LM interneurons is induced by theta patterns of stimulation

Oriens lacunosum-moleculare (O-LM) interneurons display a non-conventional form of long-term synaptic potentiation (LTP) conferred by calcium-permeable AMPA receptors (CP-AMPAR). So far, this form of LTP has been induced in O-LM cells by physiologically unrealistic protocols. We report here the induction of both synaptic and intrinsic potentiation in O-LM interneurons following stimulation of afferent glutamatergic inputs in the theta ({theta}) frequency range. LTP is induced by synaptic activation of CP-AMPAR whereas long-term potentiation of intrinsic excitability (LTP-IE) results from the mGluR1-dependent down-regulation of Kv7 voltage-dependent potassium channel and hyperpolarization activated and cyclic nucleotide-gated (HCN) channel through the depletion of phosphatidylinositol-4,5-bi-phosphate (PIP2). LTP and LTP-IE are reversible, demonstrating that both synaptic and intrinsic changes are bidirectional in O-LM cells. We conclude that physiological stimuli such as {theta} patterns induce synaptic and intrinsic potentiation in O-LM interneurons.

neuroscience↗

bioRxiv2021

An epitope specific patient-derived LGI1-autoantibody enhances neuronal excitability by modulating the Kv1.1 channel.

Leucine-rich Glioma Inactivated protein 1 (LGI1) is expressed in the central nervous and genetic loss of function is associated with epileptic disorders. Also, patients with LGI1-directed autoantibodies have frequent focal seizures as a key feature of their disease. LGI1 is composed of a Leucine Rich Repeat (LRR) and an Epitempin (EPTP) domain. These domains are reported to interact with different aspects of the transsynaptic complex formed by LGI1 at excitatory synapses, including presynaptic Kv1 potassium channels. Patient-derived monoclonal antibodies (mAbs) are ideal reagents to study whether domain-specific LGI1-autoantibodies induce epileptiform activities in neurons, and their downstream mechanisms. To address this question, we measured the intrinsic excitability of CA3 pyramidal neurons in organotypic cultures from rat hippocampus treated with either a LRR- or an EPTP-reactive patient-derived mAb. The antibodies induced changes in neuronal intrinsic excitability which led us to measure their effects on Kv1-type potassium currents. We found an increase of intrinsic excitability correlated with a reduction of the sensitivity to a selective Kv1.1-channel blocker in neurons treated with the LRR mAb compared to the control, but not in neurons treated with the EPTP mAb. Our findings suggest LRR mAbs are able to modulate neuronal excitability that could account for epileptiform activities observed in patients.

neuroscience↗

bioRxiv2021

Homeostatic regulation of axonal Kv1.1 channels accounts for both synaptic and intrinsic modifications in CA3 circuit

Homeostatic plasticity of intrinsic excitability goes hand-in-hand with homeostatic plasticity of synaptic transmission. However, the mechanisms linking the two forms of homeostatic regulation have not been identified so far. Using electrophysiological, imaging and immunohistochemical techniques, we show here that blockade of excitatory synaptic receptors for 2-3 days induces an up-regulation of synaptic strength at CA3-CA3 connexions and intrinsic excitability of CA3 pyramidal neurons. Activity-deprived connexions were found to express a high release probability, an insensitivity to dendrotoxin, and a lack of depolarization-induced presynaptic facilitation, indicating a loss of presynaptic Kv1.1 function. The down-regulation of Kv1.1 channels in activity-deprived neurons was confirmed by their broader action potentials measured in the axon that were insensitive to dendrotoxin. We conclude that regulation of axonal Kv1.1 channel constitutes a unique mechanism linking intrinsic excitability and synaptic strength that accounts for the functional synergy existing between homeostatic regulation of intrinsic excitability and synaptic transmission.

neuroscience↗

bioRxiv2021

Long-lasting reduction of intrinsic excitability in O-LM interneurons is mediated by endocannabinoid-dependent up-regulation of Kv7 channels

KCNQ-Kv7 channels are found at the axon initial segment of pyramidal neurons where they control cell firing and membrane potential. In oriens lacunosum moleculare (O-LM) interneurons, these channels are mainly expressed in the dendrites, suggesting a peculiar function of Kv7 channels in these neurons. The physiology of Kv7 channels is well characterized today but the precise contribution of these channels to neuronal plasticity is still unknown. Here, we show that Kv7 channel activity is up-regulated following induction of presynaptic long-term synaptic depression (LTD) in O-LM interneurons, thus resulting in a synergistic long-term depression of intrinsic neuronal excitability (LTD-IE). Both LTD and LTD-IE involve endocannabinoid (eCB) biosynthesis for their induction. Molecular modeling shows strong interaction of eCBs with Kv7.2/3 channel, suggesting a persistent action of these lipids on Kv7 channel activity. Our data thus unveil a major role for eCB synthesis in triggering both synaptic and intrinsic depression in O-LM interneurons.

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bioRxiv2020

Neural excitability increases with axonal resistance between soma and axon initial segment

The position of the axon initial segment (AIS) is thought to play a critical role in neuronal excitability. In particular, empirical studies have found correlations between a distal shift in AIS position and a reduction of excitability. Yet, theoretical work has suggested that the neuron should become more excitable as the distance between soma and AIS is increased, because of increased electrical isolation. Specifically, resistive coupling theory predicts that the action potential (AP) threshold decreases with the logarithm of the axial resistance (Ra) between the middle of the AIS and the soma. However, no direct experimental evidence has been provided so far to support this theoretical prediction. We therefore examined how changes in Ra at the axon hillock impact the voltage threshold (Vth) of the somatic AP in L5 pyramidal neurons. Increasing Ra by mechanically pinching the axon between the soma and the AIS was found to lower the spike threshold by ~6 mV. Conversely, decreasing Ra by replacing a weakly mobile ion (gluconate) by a highly mobile ion (chloride) elevated the spike threshold. All Ra-dependent changes in spike threshold could be reproduced in a Hodgkin-Huxley compartmental model. We conclude that in L5 pyramidal neurons, excitability increases with axial resistance, and therefore with a distal shift of the AIS.

neuroscience↗

bioRxiv2020

Altered spike timing-dependent plasticity rules in physiological calcium

Like many forms of long-term synaptic plasticity, spike-timing-dependent plasticity (STDP) depends on intracellular Ca2+ signaling for its induction. Yet, all in vitro studies devoted to STDP used abnormally high external Ca2+ concentration. We measured STDP at the CA3-CA1 hippocampal synapses under different extracellular Ca2+ concentrations and found that the sign, shape and magnitude of plasticity strongly depend on Ca2+. A pre-post protocol that results in robust LTP in high Ca2+, yielded only LTD or no plasticity in the physiological Ca2+ range. LTP could be restored by either increasing the number of post-synaptic spikes or increasing the pairing frequency. A calcium-based plasticity model in which depression and potentiation depend on post-synaptic Ca2+ transients was found to fit quantitatively all the data, provided NMDA receptor-mediated non-linearities were implemented. In conclusion, STDP rule is profoundly altered in physiological Ca2+ but specific activity regimes restore a classical STDP profile.

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bioRxiv2019

Axonal Na+ channels detect and transmit levels of input synchrony in local brain circuits

Sensory processing requires mechanisms of fast coincidence-detection to discriminate synchronous from asynchronous inputs. Spike-threshold adaptation enables such a discrimination but is ineffective in transmitting this information to the network. We show here that presynaptic axonal sodium channels read and transmit precise levels of input synchrony to the postsynaptic cell by modulating the presynaptic action potential (AP) amplitude. As a consequence, synaptic transmission is facilitated at cortical synapses when the presynaptic spike is produced by synchronous inputs. Using dual soma-axon recordings, imaging, and modeling, we show that this facilitation results from enhanced AP amplitude in the axon due to minimized inactivation of axonal sodium-channels. Quantifying local circuit activity and using network modeling, we found that spikes induced by synchronous inputs produced a larger effect on network activity than spikes induced by asynchronous inputs. Therefore, this input-synchrony dependent facilitation (ISF) may constitute a powerful mechanism regulating spike transmission.

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