Rémy Schlichter

Institut des Neurosciences Cellulaires et Intégratives

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Pierrick Poisbeau

Université de Strasbourg

Sylvain Hugel

Institut des Neurosciences Cellulaires et Intégratives

P. Feltz

Centre National de la Recherche Scientifique

Jean‐Didier Breton

Australian National University

Perrine Inquimbert

Centre National de la Recherche Scientifique

Marie José Freund‐Mercier

Centre National de la Recherche Scientifique

Jean‐Luc Rodeau

Centre National de la Recherche Scientifique

Sandra Uhl‐Bronner

Institut des Neurosciences Cellulaires et Intégratives

İY

İpek Yalçın

Institut des Neurosciences Cellulaires et Intégratives

Matilde Cordero‐Erausquin

Centre National de la Recherche Scientifique

Cooperative Institutions

Centre National de la Recherche Scientifique

Université de Strasbourg

Institut des Neurosciences Cellulaires et Intégratives

Inserm

Centre National pour la Recherche Scientifique et Technique (CNRST)

Sorbonne Université

Université Laval

Institut de Chimie

McGill University

Oregon Health & Science University

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Characterization of Functional GABAergic Synapses Formed between Rat Hypothalamic Neurons and Pituitary Intermediate Lobe Cells in Coculture: Ca²⁺Dependence of Spontaneous IPSCs

Journal of Neuroscience (1996)

Pierrick Poisbeau Frédérique René Christophe Egles Jean‐Marc Félix P. Feltz

Rat hypothalamic neurons and endocrine cells from the intermediate lobe of the pituitary were grown in dissociated coculture. Neurons positively stained with an antibody against glutamate decarboxylase established apparent contacts with the α-melanocyte-stimulating hormone-positive endocrine cells. These sites of contact were intensely labeled with an antibody against the synaptic protein synapsin I and displayed ultrastructural features characteristic of synapses. Using patch-clamp recordings, we have demonstrated that these contacts correspond to functional GABAergic synapses. The synaptic currents were blocked reversibly by bicuculline (5 μ m ) and SR95531 (5 μ m ), two competitive antagonists of the GABA A receptor. At a holding potential of −60 mV, spontaneously occurring IPSCs (s-IPSCs) had small amplitudes (10–100 pA), whereas electrically evoked IPSCs (ee-IPSCs) had amplitudes up to 1 nA. The rise times of both types of IPSCs were fast (≤1 msec), and their decaying phases were fitted in most cases with a single exponential function (time constant, 50 msec). The amplitude distribution of s-IPSCs did not reveal clear, equally spaced peaks and was little affected by tetrodotoxin, suggesting that most s-IPSCs were miniature IPSCs. Reduction of extracellular calcium concentration to 0.3 m m induced a marked decrease in s-IPSC frequency and revealed a single amplitude peak at 10 pA, suggesting that a single quantum of GABA activates 8–10 GABA A channels. Thus, our preparation might be an interesting model to study different aspects of synapse formation between a central neuron and its target as well as the fundamental mechanisms of synaptic transmission at central synapses.

Synapsin I

Tetrodotoxin

10.1523/jneurosci.16-16-04835.1996

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Citations (27)

Modulation of GABAergic Synaptic Transmission by NMDA Receptors in the Dorsal Horn of the Spinal Cord

Frontiers in Molecular Neuroscience (2022)

Benjamin Leonardon Lou Cathenaut Louise Vial-Markiewicz Sylvain Hugel Rémy Schlichter

The dorsal horn (DH) of the spinal cord is an important structure involved in the integration of nociceptive messages. Plastic changes in the properties of neuronal networks in the DH underlie the development of analgesia as well as of hyperalgesia and allodynia in acute and chronic pain states. Two key mechanisms are involved in these chronic pain states: increased electrical activities and glutamate release leading to the recruitment of NMDAr and plastic changes in the synaptic inhibition. Although: (1) the balance between excitation and inhibition is known to play a critical role in the spinal network; and (2) plastic changes in spinal excitation and inhibition have been studied separately, the relationship between these two mechanisms has not been investigated in detail. In the present work, we addressed the role of NMDA receptors in the modulation of GABAergic synaptic transmission in the DH network. Using tight-seal whole-cell recordings on adult mice DH neurons, we characterized the effect of NMDAr activation on inhibitory synaptic transmission and more especially on the GABAergic one. Our results show that, in a subset of neurons recorded in lamina II, NMDAr activation facilitates spontaneous and miniature GABAergic synaptic transmission with a target specificity on GABAergic interneurons. In contrast, NMDA reduced the mean amplitude of evoked GABAergic IPSCs. These results show that NMDAr modulate GABAergic transmission by a presynaptic mechanism of action. Using a pharmacological approach, we investigated the composition of NMDAr involved in this modulation of GABAergic synaptic transmission. We found that the NMDA-induced facilitation was mediated by the activation of NMDAr containing GluN2C/D subunits. Altogether, our results bring new insights on nociceptive information processing in the spinal cord network and plastic changes in synaptic inhibition that could underlie the development and maintenance of chronic pain.

Allodynia

Interneuron

10.3389/fnmol.2022.903087

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Citations (4)

Announcement

Neuroendocrinology (1996)

Rubén W. Carón R. P. Deis Songyun Li Georges Pelletier Antonis Makrigiannakis

10.1159/000127107

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Production of 5alpha-reduced neurosteroids is developmentally regulated and shapes GABAA miniature IPSCs in lamina II of the spinal cord

HAL (Le Centre pour la Communication Scientifique Directe) (2004)

Anne Florence Keller Jean‐Didier Breton Rémy Schlichter Pierrick Poisbeau

Lamina

Source

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Modulation of GABAergic synaptic transmission by the non-benzodiazepine anxiolytic etifoxine

Neuropharmacology (2000)

Rémy Schlichter Volodymyr Rybalchenko Pierrick Poisbeau Marc Verleye J. M. Gillardin

Anti-Anxiety Agents

Modulation (music)

10.1016/s0028-3908(99)00253-1

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Citations (105)

Electrophysiological Properties of Cultured Neonatal Rat Dorsal Horn Neurons Containing GABA and Met-Enkephalin-Like Immunoreactivity

Journal of Neurophysiology (1998)

Young‐Hwan Jo M.E. Stoeckel Rémy Schlichter

Jo, Y. H., M. E. Stoeckel, and R. Schlichter. Electrophysiological properties of cultured neonatal rat dorsal horn neurons containing GABA and met-enkephalin-like immunoreactivity. J. Neurophysiol. 79: 1583–1586, 1998. We have developed a culture of neurons dissociated from the most superficial laminae of the neonatal rat spinal cord dorsal horn (DH). By using the perforated patch-clamp technique, we distinguished four types of neurons based on their firing properties in response to intracellular injection of 900 ms lasting current pulses. Type 1 neurons were characterized by a tonic firing. Type 2 neurons displayed marked spike accommodation and fired brief (<500 ms) bursts of action potentials, whereas type 3 neurons fired a single spike. Type 4 neurons exhibited different types of firing patterns, but all of them possessed a time-dependent inwardly rectifying current activated by membrane hyperpolarization. Met-enkephalin-like immunoreactivity (met-ENK-LI) and glutamic acid decarboxylase-like immunoreactivity (GAD-LI) were colocalized in 42% of the neurons ( n = 59), which were previously identified electrophysiologically. Type 1–4 neurons represented respectively 4, 64, 20, and 12% of the population of neurons colocalizing met-ENK-LI and GAD-LI. We conclude that the electrophysiological properties of DH neurons present in our cultures are similar to those described in acute slice or hemisected spinal cord preparations and that met-ENK-LI and GABA-LI are preferentially colocalized in type 2 neurons.

Tonic (physiology)

Hyperpolarization

10.1152/jn.1998.79.3.1583

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Citations (41)

Properties of the GABA receptors located on spinal primary afferent neurones and hypophyseal neuroen-docrine cells of the rat

Neuroscience Letters (1984)

Rémy Schlichter Barbara Demeneix M. Desarmenien E Desaulles Jean‐Philippe Loeffler

GABAB receptor

Dorsal root ganglion

GABAA-rho receptor

Gamma-Aminobutyric Acid

10.1016/0304-3940(84)90523-8

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Citations (22)

Trophic effects of keratinocytes on the axonal development of sensory neurons in a coculture model

European Journal of Neuroscience (2007)

Lauriane Ulmann Jean‐Luc Rodeau Louis Danoux Jean‐Luc Contet‐Audonneau G. Pauly

The epidermis, the outermost structure of the skin, fulfils important roles as a physical barrier between the organism and its environment and as a neuroendocrine, immune and sensory organ. It is innervated by unmyelinated sensory fibres conveying nociceptive and thermoceptive information. Little is known concerning the functional interactions between these sensory fibres and the keratinocytes, which constitute 95% of the epidermal cells. We have developed a coculture model of primary rat sensory neurons and keratinocytes, as well as of equivalent cell-lines: ND7-23 neurons and A431 keratinocytes. We show that primary dorsal root ganglion neurons survive well in a standard keratinocyte reference medium containing a low concentration of calcium, but fail to extend axons. However, when neurons are cocultured with keratinocytes, axonal outgrowth is strongly stimulated. The use of a Transwell culture system indicated that the stimulation of axonal growth depends on a soluble factor secreted by keratinocytes. Axon outgrowth was also induced by nerve growth factor or brain-derived neurotrophic factor, but not by neurotrophin 3 or glial cell-derived neurotrophic factor. Neurons cocultured with keratinocytes did not change their responses to ATP, capsaicin or high potassium solution, as measured by calcium imaging. The trophic effect of keratinocytes concerned essentially a population of medium-sized (17-25 microm) neurons, some of which expressed substance P-like immunoreactivity and responded to capsaicin. Our preparation, in which cells are maintained at low external calcium concentration, could represent a useful in vitro model for characterizing the effect of skin-derived guidance and trophic factors.

Dorsal root ganglion

Capsaicin

Sensory neuron

Epidermis (zoology)

10.1111/j.1460-9568.2007.05649.x

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Citations (56)

Functional high-and low affinity agonist binding sites at native dorsal horn AMPA receptors

Neuroreport (1999)

Volodymyr Rybalchenko Rémy Schlichter

TRANSMISSION and processing of nociceptive information in the superficial dorsal horn (DH) of the spinal cord involves activation of AMPA-type glutamate receptors (AMPARs). We have studied the properties of native AMPARs in freshly dissociated laminae I–II neurones from postnatal rats using a modified form of the concentration-clamp technique for fast agonist application. Analysis of kainic acid dose–response curves showed the existence of two types of functional agonist binding sites governing AMPAR activation. These sites differ by their affinity for the agonist. Depending on the neurotransmitter concentration reached in the synaptic cleft, the relative contribution of high affinity and low affinity sites might play an important role in the shaping of AMPAR-mediated postsynaptic currents.

Kainate receptor

10.1097/00001756-199906030-00033

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Citations (3)

Spinal cord stimulation: hypotheses on the underlying mechanisms

Douleur et Analgésie (2024)

Lou Cathenaut Yohann Bohren Rémy Schlichter Sylvain Hugel

10.1684/dea.2024.0289

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