Biomedical subjects

Pierre Meyrand

Publications and source records attributed to Pierre Meyrand.

10 recordsLinked to original sources

PubMed2006

Expression of the glycinergic system during the course of embryonic development in the mouse spinal cord and its co-localization with GABA immunoreactivity.

To understand better the role of glycine and gamma-aminobutyric acid (GABA) in the mouse spinal cord during development, we previously described the ontogeny of GABA. Now, we present the ontogeny of glycine-immunoreactive (Gly-ir) somata and fibers, at brachial and lumbar levels, from embryonic day 11.5 (E11.5) to postnatal day 0 (P0). Spinal Gly-ir somata appeared at E12.5 in the ventral horn, with a higher density at the brachial level. They were intermingled with numerous Gly-ir fibers reaching the border of the marginal zone. By E13.5, at the brachial level, the number of Gly-ir perikarya sharply increased throughout the whole ventral horn, whereas the density of fibers declined in the marginal zone. In the dorsal horn, the first Gly-ir somata were then detected. From E13.5 to E16.5, at the brachial level, the density of Gly-ir cells remained stable in the ventral horn, and after E16.5 it decreased to reach a plateau. In the dorsal horn, the density of Gly-ir cells increased, and after E16.5 it remained stable. At the lumbar level, maximum expression was reached at E16.5 in both the ventral and dorsal horn. Finally, the co-localization of glycine and GABA was analyzed, in the ventral motor area, at E13.5, E15.5, and E17.5. The results showed that, regardless of developmental stage studied, one-third of the stained somata co-expressed GABA and glycine. Our data show that the glycinergic system matures 1 day later than the GABAergic system and follows a parallel spatiotemporal evolution, leading to a larger population of glycine cells in the ventral horn.

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PubMed2005

Ontogenic changes of the spinal GABAergic cell population are controlled by the serotonin (5-HT) system: implication of 5-HT1 receptor family.

During the development of the nervous system, the acquisition of the GABA neurotransmitter phenotype is crucial for neural networks operation. Although both intrinsic and extrinsic signals such as transcription factors and growth factors have been demonstrated to govern the acquisition of GABA, few data are available concerning the effects of modulatory transmitters expressed by axons that progressively invade emerging neuronal networks. Among such transmitters, serotonin (5-HT) is a good candidate because serotonergic axons innervate the entire CNS at very early stages of development. We have shown previously that descending 5-HT slows the maturation of inhibitory synaptic transmission in the embryonic mouse spinal cord. We now report that 5-HT also regulates the spatiotemporal changes of the GABAergic neuronal population in the mouse spinal cord. Using a quantitative confocal study performed on acute and cultured spinal cords, we find that the GABAergic population matures according to a similar rostrocaudal temporal gradient both in utero and in organotypic culture. Moreover, we show that 5-HT delays the appearance of the spinal GABAergic system. Indeed, in the absence of 5-HT descending inputs or exogenous 5-HT, the GABAergic population matures earlier. In the presence of exogenous 5-HT, the GABA population matures later. Finally, using a pharmacological approach, we show that 5-HT exerts its action via the 5-HT1 receptor family. Together, our data suggest that, during the course of the embryonic development, 5-HT descending inputs delay the maturation of lumbar spinal motor networks relative to brachial networks.

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PubMed2005

Electrical coupling induces bistability of rhythms in networks of inhibitory spiking neurons.

Information processing in higher brain structures is thought to rely on the synchronization of spiking neurons. Increasing evidence indicates that, within these structures, inhibitory neurons are linked by both chemical and electrical synapses. However, how synchronized states may emerge from such circuits is not fully understood. Using snail neurons interconnected through a dynamic-clamp system, we show that networks of spiking neurons linked by both reciprocal inhibition and electrical coupling can express two coexisting coordination patterns of different rhythms. One of these patterns consists of antiphase firing of the network partners whereas, in the other, neurons fire synchronously. Switching between patterns may be evoked immediately by transient stimuli, demonstrating bistability of the network. Thus electrical coupling can provide a potent way for instantaneous reconfiguration of activity patterns in inhibitory spiking networks without alteration of intrinsic network properties by modulatory processes.

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PubMed2005

Reconfiguration of multiple motor networks by short- and long-term actions of an identified modulatory neuron.

The pyloric and gastric motor pattern-generating networks in the stomatogastric ganglion of the lobster Homarus gammarus are reconfigured into a new functional circuit by burst discharge in an identified pair of modulatory projection interneurons, originally named the pyloric suppressor (PS) neurons because of their inhibitory effects on pyloric network activity. Here we elucidate the actions of the PS neurons on individual members of the neighbouring gastric circuit, as well as describing their ability to alter synaptic coupling between the two networks. PS neuron firing has two distinct effects on gastric network activity: an initial short-lasting action mediated by transient inhibition of most gastric motoneurons, followed by a long-lasting circuit activation associated with a prolonged PS-evoked depolarization of the medial gastric (MG) motoneuron and the single network interneuron, Int1. These long-lasting effects are voltage-dependent, and experiments with hyperpolarizing current injection and photoablation suggest that excitation of both the MG neuron and Int1 is critical for PS-elicited gastric network rhythmicity. In parallel, PS neuron discharge persistently (lasting several minutes) enhances the strength of an inhibitory synaptic influence of the MG neuron on the pyloric dilator (PD)-anterior burster (AB) pacemaker neurons, thereby facilitating operational fusion of the two networks. Therefore, a single modulatory neuron may influence disparate populations of neurons via a range of very different and highly target-specific mechanisms: conventional transient synaptic drive and up- or down-modulation of membrane properties and synaptic efficacy. Moreover, distinctly different time courses of these actions allow different circuit configurations to be specified sequentially by a given modulatory input.

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PubMed2004

Ontogenic changes of the GABAergic system in the embryonic mouse spinal cord.

Numerous studies have demonstrated an excitatory action of GABA early in development, which is likely to play a neurotrophic role. In order to better understand the role of GABA in the mouse spinal cord, we followed the evolution of GABAergic neurons over the course of development. We investigated, in the present study, the ontogeny of GABA immunoreactive (GABA-ir) cell bodies and fibers in the embryonic mouse spinal cord at brachial and lumbar levels. GABA-ir somata were first detected at embryonic day 11.5 (E11.5) exclusively at brachial level in the marginal zone. By E13.5, the number of GABAergic neurons sharply increased throughout the extent of the ventral horn both at brachial and lumbar level. Stained perikarya first appeared in the future dorsal horn at E15.5 and progressively invaded this area while they decreased in number in the presumed ventral gray matter. At E12.5, E13.5 and E15.5, we checked the possibility that ventral GABA-ir cells could belong to the motoneuronal population. Using a GABA/Islet-1/2 double labeling, we did not detect any double-stained neurons indicating that spinal motoneurons do not synthesize GABA during the course of development. GABA-ir fibers also appeared at the E11.5 stage in the presumptive lateral white matter at brachial level. At E12.5 and E13.5, GABA-ir fibers progressively invaded the ventral marginal zone and by E15.5 reached the dorsal marginal zone. At E17.5 and postnatal day 0 (P0), the number of GABA-ir fibers declined in the white matter. Finally, by P0, GABA immunoreactivity that delineated somata was mainly restricted to the dorsal gray matter and declined in intensity and extent. The ventral gray matter exhibited very few GABA-ir cell bodies at this neonatal stage of development. The significance of the migration of somatic GABA immunoreactivity from ventral to the dorsal gray matter is discussed.

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PubMed2004

Multiple spontaneous rhythmic activity patterns generated by the embryonic mouse spinal cord occur within a specific developmental time window.

Spontaneous rhythmic activity is a ubiquitous phenomenon in developing neural networks and is assumed to play an important role in the elaboration of mature circuitry. Here we describe the day-by-day evolution of spontaneous activity in the embryonic mouse spinal cord and show that, at a specific developmental stage, 2 distinct rhythms coexist. On embryonic days E12.5 and E13.5, we observed a single type of regularly recurring short spike-episodes synchronized across cervical, thoracic, and lumbar levels. By E14.5, in addition to this motor rhythm, another type of spontaneous synchronous activity appeared, characterized by much longer lasting episodes separated by longer time intervals. On E15.5, these long episodes disappeared. Short episodes were less numerous and more irregular except at the cervical level where a rhythm was occasionally observed. By E16.5, this cervical rhythm became more robust, whereas the lumbar level fell almost silent. Surprisingly, at E17.5, spontaneous activity resumed at caudal levels, now characterized by numerous erratic short episodes. A striking ontogenetic feature of spontaneous activity was the occurrence of long episodes only at E14.5. Although concomitant at all levels of the spinal cord, long episodes displayed different patterns along the spinal cord, with tonic firing at the thoracic level and rhythmic discharge with occasional sequences of left/right alternation at the lumbar level. Thus at E14.5, the originally synchronized network has started to segregate into more specialized subnetworks. In conclusion, this work suggests that ongoing spontaneous rhythms do not follow a smooth evolution during maturation, but rather undergo profound changes at very specific stages.

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PubMed2003

Maturation of rhythmic neural network: role of central modulatory inputs.

Modulatory systems are well known for their roles in tuning the cellular and synaptic properties in the adult neuronal networks, and play a major role in the control of the flexibility of functional outputs. However far less is known concerning their role in the maturation of neural networks during the development. In this review, using the stomatogastric nervous system of lobster, we will show that the neuromodulatory system exerts a powerful influence on developing neural networks. In the adult the number of both motor target neurons and their modulatory neurons is restricted to tens of identifiable cells. They are therefore well characterized in terms of cellular, synaptic and morphological properties. In the embryo, these target cells and their neuromodulatory population are already present from mid-embryonic life. However, the motor output generated by the system is quite different: while in the embryo all the target neurons are organized into a single network generating unique motor pattern, in the adult this population splits into two distinct networks generating separate patterns. This ontogenetic partitioning does not rely on progressive acquisition of adult properties but rather on a switch between two possible network operations. Indeed, adult networks are present early in the embryonic life but their expression is repressed by central modulatory neurons. Moreover, embryonic networks can be revealed in the adult system again by altering modulatory influences. Therefore, independently of the developmental age, two potential network phenotypes co-exist within the same neuronal architecture: when one is expressed, the other one is hidden and vice versa. These transitions do not necessarily need dramatic changes such as growth/retraction of processes, acquisition of new intra-membrane proteins etc. but rather, as shown by modelling studies, it may simply rely on a subtle tuning of pre-existing intercellular electrical coupling. This in turn suggests that progressive ontogenetic alteration may not take place at the level of the target network but rather at the level of modulatory input neurons.

Action Potentials↗

PubMed2002

Descending 5-hydroxytryptamine raphe inputs repress the expression of serotonergic neurons and slow the maturation of inhibitory systems in mouse embryonic spinal cord.

Spontaneous synchronous rhythmic activities are a common feature of immature neuronal networks. Although the mechanisms underlying such activities have been studied extensively, whether they might be controlled by modulatory information remains questionable. Here, we investigated the role of descending serotonergic (5-HT) inputs from the medulla to the spinal cord in the maturation of rhythmic activity. We found that in spinal cords maintained, as a whole, in organotypic culture without the medulla, the maturation of spontaneous activity is similar to that found in spinal cords developed in utero. Interestingly, in organotypic cultures without the medulla (i.e., devoid of descending inputs), numerous intraspinal neurons expressed 5-HT, unlike in spinal cords cultivated in the presence of the medulla or matured in utero. We demonstrated that this 5-HT expression was specifically dependent on the absence of 5-HT fibers and was repressed by 5-HT itself via activation of 5-HT(1A) receptors. Finally, to verify whether the expression of 5-HT intraspinal neurons could compensate for the lack of descending 5-HT fibers and play a role in the development of spontaneous activity, we blocked the 5-HT synthesis using p-chlorophenylalanine methyl ester in cultures devoid of the medulla. Surprisingly, we found that this pharmacological treatment did not prevent the development of spontaneous activity but accelerated the maturation of intraspinal inhibition at the studied stages. Together, our data indicate that descending 5-HT raphe inputs (1) repress the expression of spinal serotonergic neurons and (2) slow the maturation of inhibitory systems in mouse spinal cord.

Action Potentials↗

PubMed2002

Rare and spatially segregated release sites mediate a synaptic interaction between two identified network neurons.

Laser-scanning confocal microscopy (LSCM), electron microcopy (EM), and cellular electrophysiology were used in combination to study the structural basis of an inhibitory synapse between two identified neurons of the same network. To achieve this, we examined the chemical inhibitory synapse between identified neurons belonging to the lobster (Homarus gammarus) pyloric network: the pyloric dilator (PD) and the lateral pyloric (LP) neurons. In order to visualize simultaneously these two neurons, we used intrasomatic injection of Lucifer Yellow (LY) in one and rhodamine/horseradish peroxydase (HRP) in the other. Under LSCM, we found only two zones of close apposition in a restricted part of the neuritic tree of the two network neurons. Then, within these two zones, the synaptic release sites were searched using EM. To this end, photoconversion of LY with immunogold and development of HRP with DAB were performed on the previously observed preparations. Structural evidence was found for only one release site per zone. To confirm this result, and because the zones of contact were always segregated in a restricted part of the dendrites, we used laser photoablation to selectively delete, either pre- or postsynaptically, the branches on which the release sites were located. In both cases, such restrictive ablation completely abolished the functional interaction between these neurons. Our results therefore demonstrate that an inhibitory synapse that is essential for the operation of a neural network relies on only very few sites of contact localized in a highly restricted part of each neuron's dendritic arbor.

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PubMed2002

Electrical coupling can prevent expression of adult-like properties in an embryonic neural circuit.

Electrical coupling is widespread in developing nervous systems and plays a major role in circuit formation and patterning of activity. In most reported cases, such coupling between rhythmogenic neurons tends to synchronize and enhance their oscillatory behavior, thereby producing monophasic rhythmic output. However, in many adult networks, such as those responsible for rhythmic motor behavior, oscillatory neurons are linked by synaptic inhibition to produce rhythmic output with multiple phases. The question then arises whether such networks are still able to generate multiphasic output in the early stage of development when electrical coupling is abundant. A suitable model for addressing this issue is the lobster stomatogastric nervous system (STNS). In the adult animal, the STNS consists of three discrete neural networks that are comprised of oscillatory neurons interconnected by reciprocal inhibition. These networks generate three distinct rhythmic motor patterns with large amplitude neuronal oscillations. By contrast, in the embryo the same neuronal population expresses a single multiphasic rhythm with small-amplitude oscillations. Recent findings have revealed that adult-like network properties are already present early in the embryonic system but are masked by an as yet unknown mechanism. Here we use computer simulation to test whether extensive electrical coupling may be involved in masking adult-like properties in the embryonic STNS. Our basic model consists of three different adult-like STNS networks that are built of relaxation oscillators interconnected by reciprocal synaptic inhibition. Individual model cells generate slow membrane potential oscillations without action potentials. The introduction of widespread electrical coupling between members of these networks dampens oscillation amplitudes and, at moderate coupling strengths, may coordinate neuronal activity into a single rhythm with different phases, which is strongly reminiscent of embryonic STNS output. With a further increase in coupling strength, the system reaches one of two final states depending on the relative contribution of inhibition and inherent oscillatory properties within the networks: either fully synchronized and dampened oscillations, or a complete collapse of activity. Our simulations indicate that, beginning from either of these two states, the emergence of distinct adult networks during maturation may arise from a developmental decrease in electrical coupling that unmasks preexisting adult-like network properties.

Action Potentials↗