The Effect of Desflurane on Neuronal Communication at a Central Synapse

Proc. Natl. Acad. Sci. U.S.A.

Vilella

et al. 2016

Self Cite

Dynamic changes of the strength of inhibitory synapses play a crucial role in processing neural information and in balancing network activity. Here, we report that the efficacy of GABAergic connections between Golgi cells and granule cells in the cerebellum is persistently altered by the activity of glutamatergic synapses. This form of plasticity is heterosynaptic and is expressed as an increase (long-term potentiation, LTP GABA ) or a decrease (long-term depression, LTD GABA ) of neurotransmitter release. LTP GABA is induced by postsynaptic NMDA receptor activation, leading to calcium increase and retrograde diffusion of nitric oxide, whereas LTD GABA depends on presynaptic NMDA receptor opening. The sign of plasticity is determined by the activation state of target granule and Golgi cells during the induction processes. By controlling the timing of spikes emitted by granule cells, this form of bidirectional plasticity provides a dynamic control of the granular layer encoding capacity.inhibitory plasticity | heterosynaptic plasticity | cerebellum | GABA | NMDA

Section: Methodsmentioning

confidence: 99%

Heterosynaptic GABAergic plasticity bidirectionally driven by the activity of pre- and postsynaptic NMDA receptors

Mapelli

Proc. Natl. Acad. Sci. U.S.A.

Vilella

et al. 2016

Self Cite

“…In contrast with the effect induced by desflurane 29 , sevoflurane altered spontaneous IPSCs by increasing frequency (+25.5 ± 4.9%, n = 7; p < 0.01; Fig 4A,D) and peak amplitude (+87.5 ± 9.6%, n = 7; p < 0.01, Fig 4A,D). Furthermore, the presence of anesthetic did not significantly change sIPSC rise time (rise10-90; -3.9 ± 2.7 %,; n = 7; p > 0.35, Fig 4B bottom traces, Fig 4D) while slowed down the current decay (t = +15.4± 4.9% n = 7; p<0.05 Fig 4B top traces, Fig 4D) indicating that the anesthetic modified the GABAergic synaptic complex.…”

Section: Stimulation Ofmentioning

confidence: 73%

“…1A). The activation of inhibitory loops through Golgi cells did not produce significant inhibitory currents because the reversal potential of chloride was about -60 mV 28,29 . In response to a 4-pulse, 100-Hz burst ( Fig 1B), EPSCs showed the typical short-term depression pattern 30 , composed of a rapid AMPA and a slow NMDA component.…”

Section: Sevoflurane Inhibits Excitatory Neurotransmission On Granulementioning

confidence: 98%

The Effects of The General Anesthetic Sevoflurane on Neurotransmission: An Experimental and Computational Study

Mapelli

Giuliani

et al. 2020

Preprint

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The brain functions can be reversibly modulated by the action of general anesthetics. Despite a wide number of pharmacological studies an extensive analysis of the cellular determinants of anesthesia at the microcircuits level is still missing. Here, by combining patchclamp recordings and mathematical modeling, we examined the impact of sevoflurane, a general anesthetic widely employed in the clinical practice, on neuronal communication. The cerebellar microcircuit was used as a benchmark to analyze the action mechanisms of sevoflurane while a biologically realistic mathematical model was employed to explore at fine grain the molecular targets of anesthetic analyzing its impact on neuronal activity. The sevoflurane altered neurotransmission by strongly increasing GABAergic inhibition while decreasing glutamatergic NMDA activity. These changes caused a notable reduction of spike discharge in cerebellar granule cells (GrCs) following repetitive activation by excitatory mossy fibers (mfs). Unexpectedly, sevoflurane altered GrCs intrinsic excitability promoting action potential generation. Computational modelling revealed that this effect was triggered by an acceleration of persistent sodium current kinetics and by an increase in voltage dependent potassium current conductance. The overall effect was a reduced variability of GrCs responses elicited by mfs supporting the idea that sevoflurane shapes neuronal communication without silencing neural circuits.

“…It has recently been shown, in fact, that in neocortical circuits, the persistent increase of GABAergic synapses can impact output firing through a decreased spike probability and increased timing [118]. Furthermore, we have recently shown in cerebellar cortex that bidirectional plasticity of inhibitory circuits [46] contributes to control the spatial and temporal pattern activity of excitatory granule cells by sharpening center-surround structures [119] and by finely regulating the timing of first spike output through subthreshold integration processes [120].…”

Section: Learning Rules and Computational Consequences Of Inhibitorymentioning

confidence: 95%

Inhibitory Plasticity: From Molecules to Computation and Beyond

Bigiani

Porro

et al. 2020

IJMS

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Synaptic plasticity is the cellular and molecular counterpart of learning and memory and, since its first discovery, the analysis of the mechanisms underlying long-term changes of synaptic strength has been almost exclusively focused on excitatory connections. Conversely, inhibition was considered as a fixed controller of circuit excitability. Only recently, inhibitory networks were shown to be finely regulated by a wide number of mechanisms residing in their synaptic connections. Here, we review recent findings on the forms of inhibitory plasticity (IP) that have been discovered and characterized in different brain areas. In particular, we focus our attention on the molecular pathways involved in the induction and expression mechanisms leading to changes in synaptic efficacy, and we discuss, from the computational perspective, how IP can contribute to the emergence of functional properties of brain circuits.