Biology subjects

Tell, F.

Publications and source records attributed to Tell, F..

5 recordsLinked to original sources

bioRxiv2024

Postnatal Development Of Dendritic Morphology And Action Potential Shape In Rat Substantia Nigra Dopaminergic Neurons

Substantia nigra pars compacta (SNc) dopaminergic (DA) neurons are characterized by specific morphological and electrophysiological properties. First, in [~]90% of the cases, their axon arises from an axon-bearing dendrite (ABD) at highly variable distances from the soma. Second, they display a highly regular pattern of spontaneous activity (aka pacemaking) and a broad action potential (AP) that faithfully back-propagate through the entire dendritic arbor. In previous studies (Moubarak et al., 2019; Moubarak et al., 2022), we demonstrated that the presence of a high density of sodium current in the ABD and the complexity of this dendrite played a critical role in the robustness of pacemaking and setting the half-width of the AP. In the current study, we investigated the postnatal development of both morphology and AP shape in SNc DA neurons in order to determine when and how the mature electrophysiological phenotype of these neurons was achieved. To do so, we performed electrophysiological recordings of SNc DA neurons at 4 postnatal ages (P3, P7, P14, P21) and fully reconstructed their dendritic and proximal axon morphology. Our results show that several morphological parameters, including the length of the ABD, display abrupt changes between P7 and P14, such that a mature morphology is reached by P14. We then showed that AP shape followed a similar timecourse. Using realistic multicompartment Hodgkin-Huxley modeling, we then demonstrated that the rapid morpho-electrical maturation of SNc DA neurons likely arises from synergistic increases in dendritic length and in somatodendritic sodium channel density. Significance statementSubstantia nigra pars compacta (SNc) dopaminergic (DA) neurons display several morphological and electrophysiological peculiarities. For instance, their axon arises in most cases from an axon-bearing dendrite (ABD) and their action potential (AP) is broad and faithfully back-propagates through the entire dendritic tree. In the present study, we performed electrophysiological recordings, neuronal reconstruction and computational modeling to determine the postnatal development of dendritic morphology and AP shape in SNc DA neurons. We found that ABD length rapidly increases after post-natal day 7 (P7) to reach maturity by P14 and that AP shape follows a similar timecourse. Computational modeling then suggested that the achievement of a mature AP comes from synergistic increases in dendritic length and in somatodendritic sodium channel density.

neuroscience↗

bioRxiv2021

MORPHOLOGICAL DETERMINANTS OF CELL-TO-CELL VARIATIONS IN ACTION POTENTIAL DYNAMICS IN SUBSTANTIA NIGRA DOPAMINERGIC NEURONS

Action potential (AP) shape is a critical electrophysiological parameter, in particular because it strongly modulates neurotransmitter release. AP shape is also used to distinguish neuronal populations, as it greatly varies between neuronal types. For instance, AP duration ranges from hundreds of microseconds in cerebellar granule cells to 2-3 milliseconds in substantia nigra pars compacta (SNc) dopaminergic (DA) neurons. While most of this variation seems to arise from differences in the subtypes of voltage- and calcium-gated ion channels expressed, a few studies suggested that dendritic morphology may also affect AP shape. However, AP duration also displays significant variability in a same neuronal type, while the determinants of these variations are poorly known. Using electrophysiological recordings, morphological reconstructions and realistic Hodgkin-Huxley modeling, we investigated the relationships between dendritic morphology and AP shape in SNc DA neurons. In this neuronal type where the axon arises from an axon-bearing dendrite (ABD), the duration of the somatic AP could be predicted from a linear combination of the complexities of the ABD and the non-ABDs. Dendrotomy simulation and experiments showed that these correlations arise from the causal influence of dendritic topology on AP duration, due in particular to a high density of sodium channels in the somato-dendritic compartment. In addition, dendritic morphology also modulated AP back-propagation efficiency in response to barrages of EPSCs in the ABD. In line with previous findings, these results demonstrate that dendritic morphology plays a major role in defining the electrophysiological properties of SNc DA neurons and their cell-to-cell variations. SIGNIFICANCE STATEMENTAction potential (AP) shape is a critical electrophysiological parameter, in particular because it strongly modulates neurotransmitter release. AP shape (e.g. duration) greatly varies between neuronal types but also within a same neuronal type. While differences in ion channel expression seem to explain most of AP shape variation across cell types, the determinants of cell-to-cell variations in a same neuronal type are mostly unknown. We used electrophysiological recordings, neuronal reconstruction and modeling to show that, due to the presence of sodium channels in the somato-dendritic compartment, a large part of cell-to-cell variations in somatic AP duration in substantia nigra pars compacta dopaminergic neurons is explained by variations in dendritic topology.

neuroscience↗

bioRxiv2021

REFINING THE IDENTITY AND ROLE OF KV4 CHANNELS IN MOUSE SUBSTANTIA NIGRA DOPAMINERGIC NEURONS

Substantia nigra pars compacta (SNc) dopaminergic (DA) neurons display a peculiar electrical phenotype characterized in vitro by a spontaneous tonic regular activity (pacemaking activity), a broad action potential and a biphasic post-inhibitory response. Several studies in rodents have underlined the central role played by the transient A-type current (IA) in the control of pacemaking activity and post-inhibitory rebound properties, thereby influencing both DA release and the physiological response of SNc neurons to incoming inhibitory inputs. Kv4.3 potassium channels were considered to be fully responsible for IA in these neurons, their density being tightly related to pacemaking frequency. In spite of this crucial electrophysiological role, we show that Kv4.3-/- transgenic mice exhibit minor alterations in locomotion and motor learning, although no compensation by functionally overlapping ion channels is observed in Kv4.3-/- SNc DA neurons. Using antigen retrieval immunohistochemistry, we further demonstrate that Kv4.2 potassium channels are also expressed in SNc DA neurons, even though their contribution to IA appears significant only in a minority of neurons (~5-10%). Using correlative analysis on recorded electrophysiological parameters and multi-compartment modeling, we then demonstrate that, rather than its conductance level, IA gating kinetics (inactivation time constant) appear as the main biophysical property defining post-inhibitory rebound delay and pacemaking frequency. Moreover, we show that the hyperpolarization-activated current (IH) has an opposing and complementary influence on the same firing features, and that the biophysical properties of IA and IH are likely coregulated in mouse SNc DA neurons. SIGNIFICANCE STATEMENTSubstantia nigra pars compacta (SNc) dopaminergic (DA) neurons are characterized by pacemaking activity, a broad action potential and biphasic post-inhibitory response. The A-type transient potassium current (IA) plays a central role in both pacemaking activity and post-inhibitory response. While it was thought so far that Kv4.3 ion channels were fully responsible for IA, using a Kv4.3-/- transgenic mouse and antigen retrieval immunohistochemistry we demonstrate that Kv4.2 channels are also expressed in SNc DA neurons, although their contribution is significant in a minority of neurons only. Using electrophysiological recordings and computational modeling, we then demonstrate that IA gating kinetics and its functional complementarity with the hyperpolarization-activated current are major determinants of both pacemaking activity and post-inhibitory response in SNc DA neurons.

neuroscience↗

bioRxiv2019

Differential robustness to specific potassium channel deletions in midbrain dopaminergic neurons

The authors have withdrawn this preprint titled "Differential robustness to specific potassium channel deletions in midbrain dopaminergic neurons". Upon review of breeding and genotyping data, Kcnn3-/- mice could not be trusted as representative of the expected genetic deletion. As a consequence data generated from these animals do not constitute a valid description of the Kcnn3-/- genotype in dopaminergic neurons. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

neuroscience↗

bioRxiv2017

Variability of quantal NMDA to AMPA current ratio in nucleus tractus solitarii neurons

The ratio between AMPA and NMDA receptors is a key factor governing integrative and plastic properties of excitatory glutamatergic synapses. To determine whether the respective proportions of AMPA and NMDA receptors are similar or vary across a neuron's synapse, we analyzed the variability of NMDA and AMPA currents in quantal responses recorded from neurons located in the nucleus tractus solitarii. We found that the average NMDA to AMPA current ratio strongly differed between recorded neurons and that most of the intra-neuronal current ratio variability was attributable to fluctuations in NMDA current. We next performed computer simulations with a Monte Carlo model of a glutamatergic synapse to estimate the part of AMPA and NMDA currents fluctuations induced by stochastic factors. We found that NMDA current variability mainly resulted from strong channel noise with few influence of release variations. On the contrary, partly because of the presence of subconductance states, AMPA receptor channel noise was low and AMPA current fluctuations tightly reflected changes in the amount of glutamate released. We next showed that these two factors, channel noise and fluctuations in glutamate release, were sufficient to explain the observed variability of the NMDA to AMPA current ratio in quantal events recorded from the same neuron. We therefore concluded that the proportion of AMPA and NMDA receptors was similar, or roughly similar, across synapses onto the same target cell.

neuroscience↗