Biomedical subjects

Richard Robitaille

Publications and source records attributed to Richard Robitaille.

11 recordsLinked to original sources

PubMed2006

Calcium signaling in Schwann cells at synaptic and extra-synaptic sites: active glial modulation of neuronal activity.

Glial cells are widely dispersed in the central nervous system (CNS) as well as in the peripheral nervous system (PNS). In the PNS, perisynaptic Schwann cells (PSCs) are the glial cells associated with the pre- and postsynaptic elements of the neuromuscular junction (NMJ). They, as other glial cells of the CNS, respond to high-frequency motor nerve stimulation with an increase in intracellular Ca(2+). In addition to detecting and responding to neurotransmission, PSCs are involved in short-term plasticity events where they depress neurotransmission through G-protein-dependent mechanisms and potentiate synaptic activity via Ca(2+)-dependent mechanisms. In this review, we will discuss evidence that outlines the role of PSCs in short- and long-term modulation of synaptic activity. We will also emphasize present functional similarities and differences in PSC activation at different NMJs. The importance of glial-neural interactions along myelinating axons will also be discussed.

Animals↗

PubMed2006

GABAergic network activation of glial cells underlies hippocampal heterosynaptic depression.

Tetanus-induced heterosynaptic depression in the hippocampus is a key cellular mechanism in neural networks implicated in learning and memory. A growing body of evidence indicates that glial cells are important modulators of synaptic functions, but very little is known about their role in heterosynaptic plasticity. We examined the role of glial cells in heterosynaptic depression, knowing that tetanization and NMDA application caused depression of synaptic field responses (fEPSPs) and induced Ca2+ rise in glial cells. Here we report that chelating Ca2+ in a glial syncytium interfered with heterosynaptic depression and NMDA-induced fEPSP depression, suggesting that Ca2+ activation of glial cells is necessary for heterosynaptic depression. The NMDA-induced Ca2+ rise in glial cells was sensitive to tetrodotoxin and reduced by the GABAB antagonist CGP55845. Both heterosynaptic depression and simultaneous Ca2+ activation of glial cells were prevented by CGP55845, suggesting an involvement of the GABAergic network in glial activation and heterosynaptic depression. Also, the GABAB agonist baclofen caused both a Ca2+ rise in glial cells and fEPSP depression. Heterosynaptic depression, as well as NMDA- and baclofen-induced depression, were attenuated by an A1 antagonist, cyclopentyl-theophylline, whereas glial cell activation was not, indicating a role of adenosine downstream of glial activation. Finally, heterosynaptic depression requires ATP degradation because ectonucleotidase inhibitors reduced this plasticity. Our work indicates that Ca2+ activation of glial cells is necessary for heterosynaptic depression, which involves the sequential interaction of Schaffer collaterals, the GABAergic network, and glia. Thus, glial and neuronal networks are functionally associated during the genesis of heterosynaptic plasticity at mammalian central excitatory synapses.

Adenosine A1 Receptor Antagonists↗

PubMed2006

Purinergic modulation of synaptic signalling at the neuromuscular junction.

Purines have physiologically important functions throughout the nervous system. In both the central (CNS) and peripheral nervous systems (PNS), purines in the form of adenosine triphosphate and adenosine can play a number of roles in neuronal activation and inhibition. In addition, purines are known to be important for glial cell signaling in both the CNS and PNS. In the PNS, the neuromuscular junction (NMJ) is an excellent model for studying simple synaptic interactions. It is well suited to investigations of neuron-glia interactions because synaptic properties are well defined and perisynaptic Schwann cells (PSCs), glial cells at the NMJ, dynamically interact with the pre- and postsynaptic elements. At the NMJ, purines are critical for presynaptic modulation but also for neuron-glia interactions. Purines signal to PSCs through metabotropic and ionotropic receptors and activation of these receptors can have both modulatory and activating functions. This review will discuss recent developments in our understanding of purinergic modulation of the NMJ with an emphasis on the involvement of purines in neuron-glia interactions at this synapse.

Adenosine Triphosphate↗

PubMed2006

Glial cells in synaptic plasticity.

Plasticity of synaptic transmission is believed to be the cellular basis for learning and memory, and depends upon different pre- and post-synaptic neuronal mechanisms. Recently, however, an increasing number of studies have implicated a third element in plasticity; the perisynaptic glial cell. Originally glial cells were thought to be important for metabolic maintenance and support of the nervous system. However, work in the past decade has clearly demonstrated active involvement of glia in stability and overall nervous system function as well as synaptic plasticity. Through specific modulation of glial cell function, a wide variety of roles for glia in synaptic plasticity have been uncovered. Furthermore, interesting circumstantial evidence suggests a glial involvement in multiple other types of plasticity. We will discuss recent advances in neuron-glial interactions that take place during synaptic plasticity and explore different plasticity phenomena in which glial cells may be involved.

Animals↗

PubMed2006

Neuron-glia interactions at the neuromuscular synapse.

The contribution of glial cells in the regulation of the transfer of information in CNS and PNS is now increasingly recognized. Perisynaptic Schwann cells (PSCs), glial cells at the neuromuscular junction (NMJ), have proven to be an exceptionally important model for studying these roles. PSCs surround nerve terminals at the NMJ and are activated by transmitter release in a frequency-dependent manner. All of these receptors, except one type, are coupled to G proteins and can be regrouped into two categories: activators and modulators of PSCs. In the former category are muscarinic (unknown subtype) and purinergic receptors (P2X and P2Y). In the latter category are adenosine (A1), Substance P (NK-1) and CGRP receptors. All receptors coupled to G proteins induce the release of Ca2+ from internal stores. In return for this activation, PSCs modulate synaptic activity and short-term plasticity. In this review, we will focus on the role of purines in the induction of glial cell activity and their possible involvement in the modulation of synaptic transmission as a result of the synaptic-induced glial activity.

Acetylcholine↗

PubMed2005

Long-term in vivo modulation of synaptic efficacy at the neuromuscular junction of Rana pipiens frogs.

Prolonged changes in motor neurone activity can result in long-term changes in synaptic transmission. We investigated whether mechanisms commonly thought to be involved in determining synaptic efficacy of vertebrate motor neurones are involved in these long-term changes. The nerve supplying the cutaneous pectoris muscle was chronically stimulated via skin surface electrodes in freely moving frogs for 5-7 days. Chronic stimulation induced a 50% reduction in evoked endplate potential (EPP) amplitude at stimulated neuromuscular junctions (NMJs). These changes appear to be presynaptic since miniature EPP (mEPP) amplitude was unchanged while mEPP frequency was decreased by 46% and paired-pulse facilitation was increased by 26%. High frequency facilitation (40 Hz, 2 s) was also increased by 89%. Moreover, stimulated NMJs presented a 92% decrease in synaptic depression (40 Hz, 2 s). An increase in mitochondrial metabolism was observed as indicated by a more pronounced labelling of active mitochondria (Mitotracker) in stimulated nerve terminals, which could account for their greater resistance to synaptic depression. NMJ length visualized by alpha-bungarotoxin staining of nAChRs was not affected. Presynaptic calcium signals measured with Calcium Green-1 were larger in stimulated NMJs at low frequency (0.2 Hz) and not different from control NMJs at higher frequency (40 Hz, 2 s and 30 s). These results suggest that some mechanisms downstream of calcium entry are responsible for the determination of synaptic output, such as a down-regulation of some calcium-binding proteins, which could explain the observed results. The possibility of a change in frequenin expression, a calcium-binding protein that is more prominently expressed in phasic synapses, was, however, refuted by our results.

Adaptation, Physiological↗

PubMed2004

Glial modulation of synaptic transmission at the neuromuscular junction.

The neuromuscular junction (NMJ) is a cholinergic synapse that controls muscle contraction. Glial cells, called perisynaptic Schwann cells, surround nerve terminals at the NMJ. Transmitter release induced by repetitive nerve stimulation, elicit a frequency-dependent activation of G-protein-coupled receptors on perisynaptic Schwann cells and the release of calcium from internal stores. In return, perisynaptic Schwann cells modulate synaptic activity during and following high-frequency stimulation through short-term plasticity. In the present review, we discuss evidence of glial involvement in the short-term plasticity at the NMJ and the potential impact of such modulation on synaptic efficacy.

Animals↗

PubMed2003

Glial cells and neurotransmission: an inclusive view of synaptic function.

Glial cells throughout the nervous system are closely associated with synapses. Accompanying these anatomical couplings are intriguing functional interactions, including the capacity of certain glial cells to respond to and modulate neurotransmission. Glial cells can also help establish, maintain, and reconstitute synapses. In this review, we discuss evidence indicating that glial cells make important contributions to synaptic function.

Animals↗

PubMed2003

Glutamatergic modulation of synaptic plasticity at a PNS vertebrate cholinergic synapse.

The presence and the functionality of a glutamatergic regulation was studied at the frog neuromuscular junction (NMJ), a singly innervated cholinergic synapse. Bath application of glutamate reduced transmitter release without affecting nerve-evoked presynaptic Ca2+ entry and handling. (1S,3R)-aminocyclopentanedicarboxylic acid (ACPD), a metabotropic glutamate receptor (mGluR) agonist, mimicked the effects of glutamate while (S)-alpha-methyl-4-carboxyphenylglycine (MCPG), a mGluR antagonist, blocked glutamate effects. MCPG had no effect on transmitter release evoked at low frequency (0.2 Hz) but significantly reduced synaptic depression (10 Hz, 80 s). This suggests that a frequency-dependent endogenous glutamatergic modulation is present at the frog NMJ and is mediated through mGluRs. Immunohistochemical labelling revealed the presence of mGluRs at the end plate area, primarily on muscle fibers. Functional glutamate uptake machinery was also found at the NMJ as blockade of glutamate transport by the inhibitor dl-threo-beta-benzyloxyaspartate (DL-TBOA) increased high frequency-induced depression, suggesting that the transporters system is used to eliminate glutamate from the extracellular space. Moreover, immunohistochemical labelling revealed that glutamate-aspartate transporters (GLASTs) are predominantly present on perisynaptic Schwann cells (PSCs). However, local application of glutamate on PSCs unreliability evoked small Ca2+ responses. Hence, these data suggest that functional glutamatergic interactions at a purely cholinergic synapse, shape synaptic efficacy and short-term plasticity in a frequency-dependent fashion.

Acetylcholine↗

PubMed2003

Perisynaptic Schwann cells at the neuromuscular junction: nerve- and activity-dependent contributions to synaptic efficacy, plasticity, and reinnervation.

Glial cells are increasingly recognized for their important contributions to CNS and PNS synaptic function. Perisynaptic Schwann cells, which are glial cells at the neuromuscular junction, have proven to be an exceptionally useful model for studying these roles. Recent studies have shown that they detect and reciprocally modulate synaptic efficacy in an activity-dependent manner in the short term. In addition, perisynaptic Schwann cells guide reinnervating nerve sprouts after deinnervation, and many important parameters of this are dependent on synapse activity. Thus, it is hypothesized that perisynaptic Schwann cells are key integrators in a continuum of synaptic efficacy, stability, and plasticity at the neuromuscular junction, which is important for maintaining and restoring synaptic efficacy.

Animals↗

PubMedDate not supplied

Modulation of neurotransmission by reciprocal synapse-glial interactions at the neuromuscular junction.

Perisynaptic Schwann cells are glial cells that are closely associated with pre- and postsynaptic elements of the neuromuscular junction. Recent evidence shows that these cells detect and modulate neurotransmission in an activity-dependent fashion. Through G-protein signalling and Ca(2+) released from internal stores they can decrease or increase neurotransmitter release, respectively. Thus, they help to establish the level of neurotransmission associated with activity dependent short-term synaptic plasticity. We discuss evidence implicating perisynaptic Schwann cells as being active partners in neurotransmission at the neuromuscular junction, with emphasis on the modulation of short-term plasticity and potential implications for long-term changes.

Animals↗