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In Vivo Measurement of Glycine Receptor Turnover and Synaptic Size Reveals Differences between Functional Classes of Motoneurons in Zebrafish.

ABSTRACT: The interplay between binding and unbinding of synaptic receptor proteins at synapses plays an important role in determining receptor concentration and synaptic strength, with known links between changes in binding kinetics and synaptic plasticity. The regulation of such kinetics may subserve the specific functional requirements of neurons in intact circuits. However, the majority of studies of synaptic turnover kinetics have been performed in cultured neurons outside the context of normal circuits, and synaptic receptor turnover has not been measured at individual synaptic sites in vivo. We quantified the distribution of glycinergic receptor dynamics using fluorescence recovery after photoconversion of synapses in intact zebrafish and correlated recovery kinetics to synaptic volume in two functionally distinct classes of cells: primary and secondary motoneurons. The rate of fluorescence recovery after photoconversion decreased with synaptic volume in both types of motoneurons, with larger synapses having slower recovery. Primary motoneurons had both larger synapses and associated slower recovery times than secondary motoneurons. Our results suggest that synaptic kinetics are regulated in concert with synaptic sizes and reflect the functional role played by neurons within their circuit.

SUBMITTER: Chow DM

PROVIDER: S-EPMC5437745 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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In Vivo Measurement of Glycine Receptor Turnover and Synaptic Size Reveals Differences between Functional Classes of Motoneurons in Zebrafish.

Chow Dawnis M DM Zuchowski Kathryn A KA Fetcho Joseph R JR

Current biology : CB 20170413 8

The interplay between binding and unbinding of synaptic receptor proteins at synapses plays an important role in determining receptor concentration and synaptic strength, with known links between changes in binding kinetics and synaptic plasticity. The regulation of such kinetics may subserve the specific functional requirements of neurons in intact circuits. However, the majority of studies of synaptic turnover kinetics have been performed in cultured neurons outside the context of normal circu ...[more]

PMID: 28416115

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Project description:Many pentameric ligand-gated ion channels are modulated by extracellular pH. Glycine receptors (GlyRs) share this property, but it is not well understood how they are affected by pH changes. Whole cell experiments on HEK293 cells expressing zebrafish homomeric α1 GlyR confirmed previous reports that acidic pH (6.4) reduces GlyR sensitivity to glycine, whereas alkaline pH (8.4) has small or negligible effects. In addition to that, at pH 6.4 we observed a reduction in the maximum responses to the partial agonists β-alanine and taurine relative to the full agonist glycine. In cell-attached single-channel recording, low pH reduced agonist efficacy, as the maximum open probability decreased from 0.97, 0.91 and 0.66 to 0.93, 0.57 and 0.34 for glycine, β-alanine and taurine, respectively, reflecting a threefold decrease in efficacy equilibrium constants for all three agonists. We also tested the effect of pH 6.4 in conditions that replicate those at the native synapse, recording outside-out currents elicited by fast application of millisecond pulses of agonists on α1 and α1β GlyR, at a range of intracellular chloride concentrations. Acidic pH reduced the area under the curve of the currents, by reducing peak amplitude, slowing activation and speeding deactivation. Our results show that acidification of the extracellular pH by one unit, as may occur in pathological conditions such as ischaemia, impairs GlyR gating and is likely to reduce the effectiveness of glycinergic synaptic inhibition. KEY POINTS: Extracellular pH in the central nervous system (CNS) is known to shift towards acidic values during pathophysiological conditions such as ischaemia and seizures. Acidic extracellular pH is known to affect GABAergic inhibitory synapses, but its effect on signals mediated by glycine receptors (GlyR) is not well characterised. Moderate acidic conditions (pH 6.4) reduce the maximum single channel open probability of recombinant homomeric GlyRs produced by the neurotransmitter glycine or other agonists, such as β-alanine and taurine. When glycine was applied with a piezoelectric stepper to outside out patches, to simulate its fast rise and short duration at the synapse, responses became shorter and smaller at pH 6.4. The effect was also observed with physiologically low intracellular chloride and in mammalian heteromeric GlyRs. This suggests that acidic pH is likely to reduce the strength of inhibitory signalling at glycinergic synapses.

Dataset Information

In Vivo Measurement of Glycine Receptor Turnover and Synaptic Size Reveals Differences between Functional Classes of Motoneurons in Zebrafish.

Publications

In Vivo Measurement of Glycine Receptor Turnover and Synaptic Size Reveals Differences between Functional Classes of Motoneurons in Zebrafish.

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