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Biomedical subjects

Dominique Debanne

Publications and source records attributed to Dominique Debanne.

13 recordsLinked to original sources
PubMed2006

Metabotropic glutamate receptor subtype 1 regulates sodium currents in rat neocortical pyramidal neurons.

Brain sodium channels (NaChs) are regulated by various neurotransmitters such as acetylcholine, serotonin and dopamine. However, it is not known whether NaCh activity is regulated by glutamate, the principal brain neurotransmitter. We show here that activation of metabotropic glutamate receptor (mGluR) subtype 1 regulates fast transient (I(NaT)) and persistent Na(+) currents (I(NaP)) in cortical pyramidal neurons. A selective agonist of group I mGluR, (S)-3,5-dihydroxyphenylglycine (DHPG), reduced action potential amplitude and decreased I(NaT). This reduction was blocked when DHPG was applied in the presence of selective mGluR1 antagonists. The DHPG-induced reduction of the current was accompanied by a shift of both the inactivation curve of I(NaT) and the activation curve of I(NaP). These effects were dependent on the activation of PKC. The respective role of these two regulatory processes on neuronal excitability was determined by simulating transient and persistent Na(+) conductances (G(NaT) and G(NaP)) with fast dynamic-clamp techniques. The facilitated activation of G(NaP) increased excitability near the threshold, but, when combined with the down-regulation of G(NaT), repetitive firing was strongly decreased. Consistent with this finding, the mGluR1 antagonist LY367385 increased neuronal excitability when glutamatergic synaptic activity was stimulated with high external K(+). We conclude that mGluR1-dependent regulation of Na(+) current depresses neuronal excitability, which thus might constitute a novel mechanism of homeostatic regulation acting during intense glutamatergic synaptic activity.

Action Potentials↗
PubMed2006

Semaphorin3A regulates synaptic function of differentiated hippocampal neurons.

Semaphorins are major chemorepellents for developing neuronal projections. Their persistent expression at adult stages suggests that they may contribute to the functioning of neuronal circuits. We investigated the functional properties of semaphorin3A (Sema3A) in adult hippocampal neurons, and report that exogenous application of this cue decreases the efficacy of synaptic transmission evoked in the CA1 region of hippocampal slices. In situ hybridization, imaging and biochemical techniques showed that the Sema3A receptor component neuropilin-1 is present at hippocampal synapses and localizes in the presynaptic membrane. In differentiated cultured hippocampal neurons, Sema3A elicited Erk1/2 phosphorylation in somata and neuritic compartments. Furthermore, Sema3A application resulted in a striking reduction of synaptophysin and postsynaptic density 95 puncta without affecting the axon diameter. These observations reveal novel functional potentialities for secreted semaphorins, which suggest that these cues could modulate the morphology and function of synapses in the adult brain.

Animals↗
PubMed2006

A brief period of epileptiform activity strengthens excitatory synapses in the rat hippocampus in vitro.

PURPOSE: We examined here whether a very short period of epileptiform activity could produce lasting modifications of synaptic strength and network properties in the rat hippocampus in vitro. METHODS: Synaptic transmission at CA3-CA1 and at CA3-CA3 pyramidal cell synapses was monitored in hippocampal slice cultures before and after a very brief episode of epileptiform activity (20-180 s) induced with bicuculline methochloride. RESULTS: We show here that a brief period of epileptiform activity induces long-lasting potentiation of glutamatergic transmission at CA3-CA1 and at CA3-CA3 pyramidal cell synapses. This potentiation also was observed at synapses formed by pairs of monosynaptically connected neurons. It was dependent on N-methyl-d-aspartate (NMDA) receptors, occluded classic long-term potentiation, and could be depotentiated by low-frequency stimulation at 3 Hz. Recruitment of polysynaptic pathways within area CA3 was facilitated after epileptiform activity indicating that the induced potentiation enhanced overall hippocampal network excitability. CONCLUSIONS: These changes in synaptic transmission may contribute to the genesis of epilepsy and to seizure-associated memory deficits.

Animals↗
PubMed2003

Long-term enhancement of neuronal excitability and temporal fidelity mediated by metabotropic glutamate receptor subtype 5.

The cellular substrate for memory is generally attributed to long-lasting changes in synaptic strength. We report here that synaptic or pharmacological activation of the metabotropic glutamate receptor subtype 5 (mGluR5) induces long-term potentiation of intrinsic excitability (LTP-IE) in layer V pyramidal neurons. mGluR5-dependent LTP-IE was associated with a persistent reduction of the afterhyperpolarization (AHP) outward current (IAHP), resulting in the potentiation of EPSP-spike coupling. Apamin occluded induction of LTP-IE, indicating that downregulation of small conductance calcium-dependent potassium (SK) channels mediates this process. In addition to the improved reliability of the input-output function, LTP-IE led to increased temporal precision. The induced reduction of IAHP accelerated the rate of membrane depolarization preceding each action potential and subsequently decreased the jitter of the neuronal discharge. We conclude that mGluR5-dependent LTP-IE not only promotes the spread of excitation in the cortical network but also persistently enhances the temporal fidelity of the neuronal message.

Action Potentials↗
PubMed2003

A targeting motif involved in sodium channel clustering at the axonal initial segment.

The sorting of sodium channels to axons and the formation of clusters are of primary importance for neuronal electrogenesis. Here, we showed that the cytoplasmic loop connecting domains II and III of the Nav1 subunit contains a determinant conferring compartmentalization in the axonal initial segment of rat hippocampal neurons. Expression of a soluble Nav1.2II-III linker protein led to the disorganization of endogenous sodium channels. The motif was sufficient to redirect a somatodendritic potassium channel to the axonal initial segment, a process involving association with ankyrin G. Thus, this motif may play a fundamental role in controlling electrical excitability during development and plasticity.

Amino Acid Motifs↗
PubMed2003

A-, T-, and H-type currents shape intrinsic firing of developing rat abducens motoneurons.

During postnatal development, profound changes take place in the excitability of nerve cells, including modification in the distribution and properties of receptor-operated channels and changes in the density and nature of voltage-gated channels. We studied here the firing properties of abducens motoneurons (aMns) in transverse brainstem slices from postnatal day (P) 1-13 rats. Recordings were made from aMNs in the whole-cell configuration of the patch-clamp technique. Two main types of aMn could be distinguished according to their firing profile during prolonged depolarizations. Both types were identified as aMns by their fluorescence following retrograde labelling with the lipophilic carbocyanine DiI in the rectus lateralis muscle. The first type (BaMns) exhibited a burst of action potentials (APs) followed by an adaptation of discharge and were encountered in approximately 70 % of aMns. Their discharge profile resembled that of adult aMns and was encountered in all aMns after P9. BaMns exhibited a hyperpolarization-induced rebound potential that was blocked by low concentrations of Ni2+ or by Ca2+-free external solution. This current had the properties of the T-type current. Action potentials of BaMns showed a complex afterhyperpolarization (AHP). An inward rectification was evidenced following hyperpolarization and was blocked by external application of caesium or ZD7288, indicating the presence of the hyperpolarization-activated cationic current (IH). Blocking the IH current almost doubled the input resistance of BaMns. The second class of aMns (DaMns) displayed a delayed excitation that was mediated by A-type K+ currents and was observed only between P4 and P9. DaMns exhibited immature characteristics: an action potential with a simple AHP, a linear current-voltage relation and a large input resistance. The number of aMns remained unchanged when both types were present (P5-P6) and later in development when only BaMns were encountered (P19), suggesting that DaMns mature into BaMns during postnatal development. We conclude that aMns display profound reorganization in their intrinsic excitability during postnatal development.

Abducens Nerve↗
PubMed2002

Bidirectional plasticity of excitatory postsynaptic potential (EPSP)-spike coupling in CA1 hippocampal pyramidal neurons.

Integration of synaptic excitation to generate an action potential (excitatory postsynaptic potential-spike coupling or E-S coupling) determines the neuronal output. Bidirectional synaptic plasticity is well established in the hippocampus, but whether active synaptic integration can display potentiation and depression remains unclear. We show here that synaptic depression is associated with an N-methyl-d-aspartate receptor-dependent and long-lasting depression of E-S coupling. E-S depression is input-specific and is expressed in the presence of gamma-aminobutyric acid type A and B receptor antagonists. In single neurons, E-S depression is observed without modification of postsynaptic passive properties. We conclude that a decrease in intrinsic excitability underlies E-S depression and is synergic with glutamatergic long-term depression.

Animals↗
PubMed2002

GABA and glycine co-release optimizes functional inhibition in rat brainstem motoneurons in vitro.

Whole-cell patch clamp recordings of miniature inhibitory postsynaptic currents (mIPSCs) were obtained in identified abducens motoneurons (aMns) from young rats (P5-P13). Three types of mIPSC were distinguished according to their kinetics and their sensitivity to receptor antagonists: faster decaying events mediated by glycine receptors (glyRs), slower decaying events mediated by GABA(A) receptors (GABA(A)Rs), and mIPSCs displaying two components corresponding to GABA and glycine co-release. Dual component events accounted for approximately 30 % of mIPSCs, independently of the rat's age and were also identified during evoked transmitter release. In contrast, the kinetics of glyR- and GABA(A)R-mediated mIPSCs became faster during development. Monosynaptic inhibitory postsynaptic potentials (IPSPs) were able to fully inhibit motoneuron discharge elicited by current pulses. When the GABA(A)R-mediated component or the glyR-mediated component of the IPSP was blocked, the inhibition of motoneuron firing was reduced. The 20-80 % rise time and duration of GABA(A)R-mediated IPSPs were significantly longer than those mediated by glyRs. The time window of inhibition for each component was determined using single postsynaptic action potentials elicited with various delays from the onset of the IPSP. GlyR-mediated IPSPs induced fast transient inhibition whereas GABA(A)R-mediated IPSPs induced slow sustained suppression of firing. Using a modelling approach, we found that the two components summated non-linearly. We conclude that in developing aMns, co-release of GABA and glycine determines the strength and timing of inhibition through non-linear interactions between the two components, thus optimizing inhibition of motoneuron function.

Animals↗
PubMedDate not supplied

Brain plasticity and ion channels.

It is generally believed that spatio-temporal configurations of distributed activity in the brain contribute to the coding of neuronal information and that synaptic contacts between nerve cells could play a central role in the formation of privileged pathways of activity. Synaptic plasticity is not the only mode of regulation of information processing in the brain and persistent regulations of ionic conductances in some specialized neuronal areas such as the dendrites, the cell body and the axon could also modulate, in the short- and the long-term, the propagation of information in the brain. Persistent changes in intrinsic excitability have been reported in several brain areas in which activity is modified during a classical conditioning. The role of synaptic activity seems to be determinant in the induction but the learning rules and the underlying mechanisms remain to be defined. This review discusses the role of neuronal activity in the induction of intrinsic plasticity in cortical, hippocampal and cerebellar neurons. Activation and inactivation properties of ionic channels in the axon determine the short-term dynamics of axonal propagation and synaptic transmission. Activation of glutamate receptors initiates a long-term modification in neuronal excitability that may represent the substrate for the mnesic engram and for the stabilization of the epileptic state. Similarly to synaptic plasticity, long-lasting intrinsic plasticity appears to be reversible and to express a certain level of input or cellular specificity. These non-synaptic forms of plasticity affect the signal propagation in the axon, the dendrites and the soma. They not only share common learning rules and induction pathways with the better known synaptic plasticity such as NMDA receptor-dependent LTP and LTD but also contribute in synergy with these synaptic changes to the formation of a coherent mnesic engram.

Animals↗
PubMedDate not supplied

Long-term plasticity of intrinsic excitability: learning rules and mechanisms.

Spatio-temporal configurations of distributed activity in the brain is thought to contribute to the coding of neuronal information and synaptic contacts between nerve cells could play a central role in the formation of privileged pathways of activity. Synaptic plasticity is not the exclusive mode of regulation of information processing in the brain, and persistent regulations of ionic conductances in some specialized neuronal areas such as the dendrites, the cell body, and the axon could also modulate, in the long-term, the propagation of neuronal information. Persistent changes in intrinsic excitability have been reported in several brain areas in which activity is elevated during a classical conditioning. The role of synaptic activity seems to be a determinant in the induction, but the learning rules and the underlying mechanisms remain to be defined. We discuss here the role of synaptic activity in the induction of intrinsic plasticity in cortical, hippocampal, and cerebellar neurons. Activation of glutamate receptors initiates a long-term modification in neuronal excitability that may represent a parallel, synergistic substrate for learning and memory. Similar to synaptic plasticity, long-lasting intrinsic plasticity appears to be bidirectional and to express a certain level of input or cell specificity. These nonsynaptic forms of plasticity affect the signal propagation in the axon, the dendrites, and the soma. They not only share common learning rules and induction pathways with the better-known synaptic plasticity such as NMDA receptor dependent LTP and LTD, but also contribute in synergy with these synaptic changes to the formation of a coherent engram.

Action Potentials↗