Biology subjects

Fronzaroli-Molinieres, L.

Publications and source records attributed to Fronzaroli-Molinieres, L..

5 recordsLinked to original sources

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↗

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.

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↗

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.

neuroscience↗