In vivolong-term synaptic plasticity of glial cells

Abstract

Evidence showing the ability of glial cells to detect, respond to and modulate synaptic transmission and plasticity has contributed to the notion of glial cells as active synaptic partners. However, synaptically induced plasticity of glia themselves remains ill defined. Here we used the amphibian neuromuscular junction (NMJ) to study plasticity of perisynaptic Schwann cells (PSCs), glial cells at this synapse, following long-term in vivo modifications of synaptic activity. We used two models that altered synaptic activity in different manners. First, chronic blockade of postsynaptic nicotinic receptors using α-bungarotoxin (α-BTx) decreased facilitation, increased synaptic depression and decreased post-tetanic potentiation (PTP). Second, chronic nerve stimulation increased facilitation and resistance to synaptic depression, while leaving PTP unaltered. Our results indicate that there is no direct relationship between transmitter release and PSC calcium responses. Indeed, despite changes in transmitter release and plasticity in stimulated NMJs, nerve-evoked PSC calcium responses were similar to control. Similarly, PSC calcium responses in α-BTx treated NMJs were delayed and smaller in amplitude, even though basal level of transmitter release was increased. Also, when isolating purinergic and muscarinic components of PSC calcium responses, we found an increased sensitivity to ATP and a decreased sensitivity to muscarine in chronically stimulated NMJs. Conversely, in α-BTx treated NMJs, PSC sensitivity remained unaffected, but ATP-and muscarine-induced calcium responses were prolonged. Thus, our results reveal complex modifications of PSC properties, with differential modulation of signalling pathways that might underlie receptor regulation or changes in Ca 2+ handling. Importantly, similar to neurons, perisynaptic glial cells undergo plastic changes induced by altered synaptic activity. IntroductionThere is now a growing body of evidence indicating that glial cells play an active role in synaptic communication throughout the nervous system. They are indeed involved in the regulation of synaptic transmission and plasticity (reviewed by Auld & Robitaille, 2003;Halassa et al. 2007), believed to be the functional basis of learning and memory. Hence, glial cells are full participants at synapses and contribute actively to neuronal processing and integration. Complementary to their active role in regulating synaptic plasticity, glial cells themselves exhibit activity-dependent changes in their properties during development (Pasti et al. 1997). However, there is no direct evidence that glial cell modifications are specific and adapted to the level of synaptic activity and that they can occur in mature systems. Such adaptation, concomitant with pre-and postsynaptic plasticity, would be essential to maintain appropriate communication between all components of the tripartite synapse. Hence, the goal of this work was to test whether the properties and activation of perisynaptic glial cells are differentially regulated in re...

A protein synthesis and nitric oxide-dependent presynaptic enhancement in persistent forms of long-term potentiation

“…Alternatively, NO may act on astrocytes or other intermediary cells that then initiate signaling to the presynaptic neuron. Indeed, there is increasing evidence to support a role for astrocytes in the regulation of LTP in culture and slice preparations (Filosa et al 2009;Bélair et al 2010;Henneberger et al 2010). Although it is possible that NO is acting post-synaptically to prolong LTP (Ko and Kelly 1999) it seems unlikely in our experiments given the concomitant inhibition of the LTP-associated presynaptic enhancement by NO antagonists.…”

New perspectives on amyotrophic lateral sclerosis: the role of glial cells at the neuromuscular junction

“…Furthermore, similar to neurons, changes in synaptic activity trigger dynamic and plastic changes in PSC properties, especially muscarinic sensitivity (Belair et al . ), suggesting that PSC activity and properties are adaptable to a given synaptic environment.…”

“…That is to say that it reflects the ability of PSCs to distinguish differences of synaptic strength between two competing nerve terminals at the same NMJ (Darabid et al 2013), or two different types of NMJs (fast and slow) (Rousse et al 2010), or even detect different patterns of neuronal activity (Todd et al 2010). Furthermore, similar to neurons, changes in synaptic activity trigger dynamic and plastic changes in PSC properties, especially muscarinic sensitivity (Belair et al 2010), suggesting that PSC activity and properties are adaptable to a given synaptic environment.…”

Neuron–glia interactions: the roles of Schwann cells in neuromuscular synapse formation and function

“…The complexity of Schwann cell modulation is underlined in the study examining the glial response to altered long-term activity. Chronic blockade of postsynaptic AChR using α -bungarotoxin or chronic nerve stimulation, surprisingly, do not affect terminal Schwann cell Ca 2+ responses [76]. However, further analysis has revealed complex changes in sensitivities to muscarinic and purinergic components in the terminal Schwann cells [76].…”

“…Chronic blockade of postsynaptic AChR using α -bungarotoxin or chronic nerve stimulation, surprisingly, do not affect terminal Schwann cell Ca 2+ responses [76]. However, further analysis has revealed complex changes in sensitivities to muscarinic and purinergic components in the terminal Schwann cells [76]. Therefore the altered long-term activities do cause the changes in how Schwann cells respond to synaptic transmission, but these changes are not revealed by the overall Ca 2+ responses in the Schwann cells.…”