Plasticité de l'excitabilité des neurones de la région CA1 de rat

It has been previously shown in pyramidal neurons of CA1 that in addition to long term synaptic plasticity, tetanus protocols (HFS/LFS) of afferent input induced a synergic plasticity of integration of synaptic potentials. In this context, we have addressed the following questions: 1) are changes on dendritic integration associated to STDP? 2) what are the mechanisms of facilitation of integration expression observed after LTP? and 3) does synaptic activity also induce persistent changes in excitability of GABAergic interneurones?Our results show that the STDP rule defined for synaptic plasticity is also valid for plasticity of integration and perfectly describes the changes in the amplitude-slope relation of the EPSP observed in parallel. These changes are input specific and require NMDA receptor activation.Plasticity of integration involves modifications of voltage-gated ions channels present at the neuronal surface. A local dendritic, NMDAR-dependent reduction of Ih current is observed during the increase in integration associated to LTP. In the presence of pharmacological blockers of Ih, LTP is still induced but facilitation of integration is no more observed. Finally, an increase in integration similar to that observed after LTP is induced when h conductance is reduced in the dendrite by using the Fast Dynamic Clamp technique. Changes in neuronal excitability is not limited to pyramidal neurons and we show that an increase in intrinsic excitability, dependent upon type I mGluR activation, is also observed in some interneurons of CA1 after HFS. This increase in excitability probably maintains the balance between excitation and inhibition in the hippocampic network by facilitating the recruitment of interneurons after hyperactivity.Our results show that in addition to changes in synaptic efficacy, change in intrinsic plasticity participate to long-lasting storage processes and probably maintain neuronal activity in a physiological range.Il a été préalablement montré dans les neurones pyramidaux de CA1 qu'en plus d'une plasticité synaptique à long terme, les protocoles de tétanisation des afférences (HFS/LFS) induisent une plasticité synergique de l'intégration des messages synaptiques. Dans ce contexte, nous avons abordé les questions suivantes: 1) des changements d'intégration dendritiques sont-ils associés à la STDP ? 2) quels sont les mécanismes d'expression de la facilitation de l'intégration observée après la LTP ? et 3) dans quelle mesure l'activité synaptique induit des changements persistants de l'excitabilité des interneurones GABAergiques ?Nos résultats montrent que la règle préétablie de STDP pour la plasticité synaptique est aussi valide pour la plasticité de l'intégration et décrit aussi parfaitement les changements de la relation amplitude/pente des PPSE observés en parallèle. Ces changements sont spécifiques de la voie synaptique activée et nécessitent l'activation des récepteurs NMDA. La plasticité de l'intégration met en jeu une régulation des conductances voltage-dépendantes présentes à la surface neuronale. Une réduction locale dendritique, NMDAR-dépendante du courant Ih est observée lors de l'augmentation d'intégration associée à la LTP. En présence de bloqueurs pharmacologiques du courant Ih, la LTP est toujours présente mais la facilitation de l'intégration n'est plus observée. Finalement, une facilitation de l'intégration similaire à celle observée après induction de la LTP est induite quand la conductance h est réduite dans la dendrite par la technique de courant imposé dynamique en temps réel.Des changements de l'excitabilité neuronale ne sont pas restreints aux neurones pyramidaux et nous montrons qu'une augmentation de l'excitabilité intrinsèque, dépendante des récepteurs mGluR de type I est également observée dans certains interneurones GABAergiques de CA1 après une HFS. Cette augmentation d'excitabilité pourrait permettre de maintenir l‘équilibre entre excitation et inhibition au sein du réseau hippocampique en facilitant le recrutement des interneurones à la suite d'épisodes d'hyperactivité.Nos résultats montrent donc qu'en parallèle des modifications de l'efficacité synaptique, des modifications de l'excitabilité intrinsèque des neurones peuvent participer au processus de stockage de l'information et permettent également de maintenir l'activité neuronale à un niveau physiologique

Enhanced Intrinsic Excitability in Basket Cells Maintains Excitatory-Inhibitory Balance in Hippocampal Circuits

SummaryThe dynamics of inhibitory circuits in the cortex is thought to rely mainly on synaptic modifications. We challenge this view by showing that hippocampal parvalbumin-positive basket cells (PV-BCs) of the CA1 region express long-term (>30 min) potentiation of intrinsic neuronal excitability (LTP-IEPV-BC) upon brief repetitive stimulation of the Schaffer collaterals. LTP-IEPV-BC is induced by synaptic activation of metabotropic glutamate receptor subtype 5 (mGluR5) and mediated by the downregulation of Kv1 channel activity. LTP-IEPV-BC promotes spiking activity at the gamma frequency (∼35 Hz) and facilitates recruitment of PV-BCs to balance synaptic and intrinsic excitation in pyramidal neurons. In conclusion, activity-dependent modulation of intrinsic neuronal excitability in PV-BCs maintains excitatory-inhibitory balance and thus plays a major role in the dynamics of hippocampal circuits

Plasticité intrinsèque des neurones de la région CA1 de l'hippocampe de rat

Parallèlement à la plasticité synaptique, l activité neuronale induit des changements d excitabilité intrinsèque (EI) des neurones et donc des propriétés d intégration. Dans les neurones pyramidaux CA1 de l hippocampe, les changements de transmission synaptique et d intégration suivent les mêmes les règles de plasticité. L un des mécanismes responsable de cette plasticité de l intégration met en jeu les conductances voltage dépendantes. Nous avons mis en évidence le rôle du courant Ih dans l augmentation de l intégration associée à la LTP. Une augmentation d EI est également observée dans certains interneurones GABAergiques de CA1 après une HFS, permettant ainsi de maintenir la balance excitation/inhibition. Nos résultats montrent donc qu en parallèle des modifications de l efficacité synaptique, des changements d EI des neurones peuvent participer au processus de stockage de l information et permettent également de maintenir l activité neuronale à un niveau physiologique.In parallel to synaptic activity, neuronal activity induces modifications in intrinsic excitability (IE) of neurons and so properties of integration. In CA1 hippocampal pyramidal neurons, changes in synaptic transmission and integration follow the same common learning rule. One of the mechanisms accountable to this plasticity of integration involves voltage-gated ions channels. We have demonstrated the role of the Ih current in the potentiation of integration associated to LTP. An increase in IE is also observed in some GABAergic interneurons after HFS, allowing the maintenance of the excitation/inhibition balance. Our results show that in addition to modification of synaptic efficacy, changes of the neurons IE participate to long-lasting storage processes and probably maintain neuronal activity in a physiological range.AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

Axon Physiology

International audienceAxons are generally considered as reliable transmission cables in which stable propagation occurs once an action potential is generated. Axon dysfunction occupies a central position in many inherited and acquired neurological disorders that affect both peripheral and central neurons. Recent findings suggest that the functional and computational repertoire of the axon is much richer than traditionally thought. Beyond classical axonal propagation, intrinsic voltage-gated ionic currents together with the geometrical properties of the axon determine several complex operations that not only control signal processing in brain circuits but also neuronal timing and synaptic efficacy. Recent evidence for the implication of these forms of axonal computation in the short-term dynamics of neuronal communication is discussed. Finally, we review how neuronal activity regulates both axon morphology and axonal function on a long-term time scale during development and adulthood

Downregulation of Dendritic Ih in CA1 Pyramidal Neurons after LTP

International audienceHyperpolarization-activated (h)-channels occupy a central position in dendritic function. Although it has been demonstrated that these channels are upregulated after large depolarizations to reduce dendritic excitation, it is not clear whether they also support other forms of long-term plasticity. We show here that nearly maximal long-term potentiation (LTP) induced by theta-burst pairing produced upregulation in h-channel activity in CA1 pyramidal neurons. In contrast, moderate LTP induced by spike-timing-dependent plasticity or high-frequency stimulation (HFS) downregulated the h-current (Ih) in the dendrites. After HFS-induced LTP, the h-conductance (Gh) was reduced without changing its activation. Pharmacological blockade of Ih had no effect on LTP induction, but occluded EPSP-to-spike potentiation, an input-specific facilitation of dendritic integration. Dynamic-clamp reduction of Gh locally in the dendrite mimicked the effects of HFS and enhanced synaptic integration in an input-selective way. We conclude that dendritic Ih is locally downregulated after induction of nonmaximal LTP, thus facilitating integration of the potentiated input

Downregulation of Dendritic Ih in CA1 Pyramidal Neurons after LTP

International audienceHyperpolarization-activated (h)-channels occupy a central position in dendritic function. Although it has been demonstrated that these channels are upregulated after large depolarizations to reduce dendritic excitation, it is not clear whether they also support other forms of long-term plasticity. We show here that nearly maximal long-term potentiation (LTP) induced by theta-burst pairing produced upregulation in h-channel activity in CA1 pyramidal neurons. In contrast, moderate LTP induced by spike-timing-dependent plasticity or high-frequency stimulation (HFS) downregulated the h-current (Ih) in the dendrites. After HFS-induced LTP, the h-conductance (Gh) was reduced without changing its activation. Pharmacological blockade of Ih had no effect on LTP induction, but occluded EPSP-to-spike potentiation, an input-specific facilitation of dendritic integration. Dynamic-clamp reduction of Gh locally in the dendrite mimicked the effects of HFS and enhanced synaptic integration in an input-selective way. We conclude that dendritic Ih is locally downregulated after induction of nonmaximal LTP, thus facilitating integration of the potentiated input

Presynaptic GABA A receptors enhance transmission and LTP induction at hippocampal mossy fiber synapses

Presynaptic GABA A receptors (GABA A Rs) occur at hippocampal mossy fiber synapses. Whether and how they modulate orthodromic signaling to postsynaptic targets is poorly understood. We found that an endogenous neurosteroid that is selective for high-affinity subunit-containing GABA A Rs depolarized rat mossy fiber boutons, enhanced action potential-dependent Ca 2+ transients and facilitated glutamatergic transmission to pyramidal neurons. Conversely, blocking GABA A Rs hyperpolarized mossy fiber boutons, increased their input resistance, decreased spike width and attenuated action potential-dependent presynaptic Ca 2+ transients, indicating that a subset of presynaptic GABA receptors are tonically active. Blocking GABA A Rs also interfered with the induction of long-term potentiation at mossy fiber-CA3 synapses. Presynaptic GABA A Rs therefore facilitate information flow to the hippocampus both directly and by enhancing LTP. © 2010 Nature America, Inc. All rights reserved.This work was supported by the Medical Research Council (UK), the Wellcome Trust, the European Research Council and the Fondation pour la Recherche Médicale (France).Peer Reviewe

The role of hyperpolarization-activated cationic current in spike-time precision and intrinsic resonance in cortical neurons in vitro

International audienceHyperpolarization-activated cyclic nucleotide modulated current (I h) sets resonance frequency within the θ-range (5–12 Hz) in pyramidal neurons. However, its precise contribution to the temporal fidelity of spike generation in response to stimulation of excitatory or inhibitory synapses remains unclear. In conditions where pharmacological blockade of I h does not affect synaptic transmission, we show that postsynaptic h-channels improve spike time precision in CA1 pyramidal neurons through two main mechanisms. I h enhances precision of excitatory post-synaptic potential (EPSP)–spike coupling because I h reduces peak EPSP duration. I h improves the precision of rebound spiking following inhibitory postsynaptic potentials (IPSPs) in CA1 pyramidal neurons and sets pacemaker activity in stratum oriens interneurons because I h accelerates the decay of both IPSPs and after-hyperpolarizing potentials (AHPs). The contribution of h-channels to intrinsic resonance and EPSP waveform was comparatively much smaller in CA3 pyramidal neurons. Our results indicate that the elementary mechanisms by which postsynaptic h-channels control fidelity of spike timing at the scale of individual neurons may account for the decreased theta-activity observed in hippocampal and neocortical networks when h-channel activity is pharmacologically reduced