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Slow glycinergic transmission mediated by transmitter pooling.

Balakrishnan V, Kuo SP, Roberts PD, Trussell LO - Nat. Neurosci. (2009)

Bottom Line: We found an exception at glycinergic synapses on granule cells of the rat dorsal cochlear nucleus.These effects could be explained by unique features of GlyRs that are activated by pooling of glycine across synapses.Thus, temporal properties of inhibition can be controlled by activity levels in multiple presynaptic cells or by adjusting release probability at individual synapses.

View Article: PubMed Central - PubMed

Affiliation: Oregon Hearing Research Center, 3181 S.W. Sam Jackson Park Road, Portland, Oregon 97239, USA.

ABSTRACT
Most fast-acting neurotransmitters are rapidly cleared from synaptic regions. This feature isolates synaptic sites, rendering the time course of synaptic responses independent of the number of active synapses. We found an exception at glycinergic synapses on granule cells of the rat dorsal cochlear nucleus. Here the duration of inhibitory postsynaptic currents (IPSCs) was dependent on the number of presynaptic axons that were stimulated and on the number of vesicles that were released from each axon. Increasing the stimulus number or frequency, or blocking glycine uptake, slowed synaptic decays, whereas a low-affinity competitive antagonist of glycine receptors (GlyRs) accelerated IPSC decay. These effects could be explained by unique features of GlyRs that are activated by pooling of glycine across synapses. Functionally, increasing the number of IPSPs markedly lengthened the period of spike inhibition following the cessation of presynaptic stimulation. Thus, temporal properties of inhibition can be controlled by activity levels in multiple presynaptic cells or by adjusting release probability at individual synapses.

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Granule cells in the dorsal cochlear nucleus (DCN) and their glycinergic postsynaptic currents(a) Schematic representation of the cochlear nucleus in a coronal brainstem slice, showing the distribution of granule cells (circles) in the DCN and the granule cell region (Grc). (b) Synaptic inputs to granule cells. Granule cells receive excitatory inputs through mossy fibers and the unipolar brush cells (UBC). Inhibitory inputs are assumed to be from the Golgi/stellate neurons. (c) Averaged glycinergic IPSC from a granule cell under control conditions and in 0.5 μM strychnine application. (d) Example traces of glycinergic IPSCs upon synaptic stimulation. Two sample IPSCs of different size are shown in thick and thin black lines. On the right, these IPSCs were normalized and their corresponding weighted decay times are shown. (e) The weighted decay constants of the IPSCs positively correlated with the amplitude. Plot show the values from three cells and their corresponding regression line. The linear fits in the three plots have r=0.92, 0.68 and 0.76 with P<0.0001 for all. (f) IPSC rise times and amplitudes had no correlation. The values from three cells, plotted as rise time and amplitude. Linear fits are insignificant for all cells. (g) Example IPSCs evoked at various voltages. The inset shows the traces normalized, revealing that responses to smaller stimuli decay more quickly. (h) Correlation of amplitude and weighted decay as stimulus strength was changed in four neurons. Correlation coefficients were 0.88, 0.91, 0.93, 0.99 (P<0.002). (i) Normalized amplitudes of responses were grouped into upper, middle, and lower thirds of the population, and their corresponding decay times averaged (9 cells, 15-36 measurements/category, P<0.002 between categories). (j) Examples of glycinergic IPSCs evoked with one and ten stimuli (10 ms interval). (k) Weighted decay times of the IPSCs against number of stimuli (100 Hz) from five cells. (l) Ten IPSCs delivered at 20 Hz and 200 Hz. (m) Weighted decay times from 7 cells at different frequencies. Comparison of decay times at different frequencies: 20-50 Hz; P<0.01, 50-100 Hz; P<0.05, 100-200 Hz; P < 0.001). Error bars are ±SEM.
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Figure 1: Granule cells in the dorsal cochlear nucleus (DCN) and their glycinergic postsynaptic currents(a) Schematic representation of the cochlear nucleus in a coronal brainstem slice, showing the distribution of granule cells (circles) in the DCN and the granule cell region (Grc). (b) Synaptic inputs to granule cells. Granule cells receive excitatory inputs through mossy fibers and the unipolar brush cells (UBC). Inhibitory inputs are assumed to be from the Golgi/stellate neurons. (c) Averaged glycinergic IPSC from a granule cell under control conditions and in 0.5 μM strychnine application. (d) Example traces of glycinergic IPSCs upon synaptic stimulation. Two sample IPSCs of different size are shown in thick and thin black lines. On the right, these IPSCs were normalized and their corresponding weighted decay times are shown. (e) The weighted decay constants of the IPSCs positively correlated with the amplitude. Plot show the values from three cells and their corresponding regression line. The linear fits in the three plots have r=0.92, 0.68 and 0.76 with P<0.0001 for all. (f) IPSC rise times and amplitudes had no correlation. The values from three cells, plotted as rise time and amplitude. Linear fits are insignificant for all cells. (g) Example IPSCs evoked at various voltages. The inset shows the traces normalized, revealing that responses to smaller stimuli decay more quickly. (h) Correlation of amplitude and weighted decay as stimulus strength was changed in four neurons. Correlation coefficients were 0.88, 0.91, 0.93, 0.99 (P<0.002). (i) Normalized amplitudes of responses were grouped into upper, middle, and lower thirds of the population, and their corresponding decay times averaged (9 cells, 15-36 measurements/category, P<0.002 between categories). (j) Examples of glycinergic IPSCs evoked with one and ten stimuli (10 ms interval). (k) Weighted decay times of the IPSCs against number of stimuli (100 Hz) from five cells. (l) Ten IPSCs delivered at 20 Hz and 200 Hz. (m) Weighted decay times from 7 cells at different frequencies. Comparison of decay times at different frequencies: 20-50 Hz; P<0.01, 50-100 Hz; P<0.05, 100-200 Hz; P < 0.001). Error bars are ±SEM.

Mentions: Glycinergic synapses mediate rapid transmission in the brainstem and spinal cord, with typical IPSC decay times of only a few ms 17. Glycine receptors (GlyRs) feature multiple binding sites, and their occupancy has distinctive effects upon gating kinetics 18-20. Well-timed glycinergic inhibition plays a crucial role in determining the synaptic output in several brain regions, particularly in the auditory system, where the precise timing of inhibition is critical to information processing 21. It is generally believed that the decay of glycinergic synaptic currents solely reflects the burst or open duration of GlyR channels 5, 6, 20, 22. The relatively incomplete desensitization exhibited by GlyRs 5, 23 and the slow turnover rates of neurotransmitter transporters 24, 25 suggests the possibility that clearance might determine IPSC decay in some cases. We studied the determinants of glycinergic IPSCs decay in granule cells of the dorsal cochlear nucleus (DCN). The DCN is a laminated structure resembling the cerebellar cortex, in which glycinergic and glutamatergic synaptic activity controls the convergence and plasticity of different sensory streams 26 (Fig 1a,b). DCN granule cells receive strong glycinergic input presumably from Golgi and/or stellate cells 27. In contrast to the rapid decays of most glycinergic IPSCs, typically just a few ms in the adult auditory brainstem 28, 29, glycinergic events last more than 10-times longer in granule cells 27. Varying the frequency and intensity of exocytosis, and interfering with glycine-receptor interactions with a low-affinity competitive antagonist, revealed that transmitter pooling controls the duration of inhibition in an activity-dependent manner.


Slow glycinergic transmission mediated by transmitter pooling.

Balakrishnan V, Kuo SP, Roberts PD, Trussell LO - Nat. Neurosci. (2009)

Granule cells in the dorsal cochlear nucleus (DCN) and their glycinergic postsynaptic currents(a) Schematic representation of the cochlear nucleus in a coronal brainstem slice, showing the distribution of granule cells (circles) in the DCN and the granule cell region (Grc). (b) Synaptic inputs to granule cells. Granule cells receive excitatory inputs through mossy fibers and the unipolar brush cells (UBC). Inhibitory inputs are assumed to be from the Golgi/stellate neurons. (c) Averaged glycinergic IPSC from a granule cell under control conditions and in 0.5 μM strychnine application. (d) Example traces of glycinergic IPSCs upon synaptic stimulation. Two sample IPSCs of different size are shown in thick and thin black lines. On the right, these IPSCs were normalized and their corresponding weighted decay times are shown. (e) The weighted decay constants of the IPSCs positively correlated with the amplitude. Plot show the values from three cells and their corresponding regression line. The linear fits in the three plots have r=0.92, 0.68 and 0.76 with P<0.0001 for all. (f) IPSC rise times and amplitudes had no correlation. The values from three cells, plotted as rise time and amplitude. Linear fits are insignificant for all cells. (g) Example IPSCs evoked at various voltages. The inset shows the traces normalized, revealing that responses to smaller stimuli decay more quickly. (h) Correlation of amplitude and weighted decay as stimulus strength was changed in four neurons. Correlation coefficients were 0.88, 0.91, 0.93, 0.99 (P<0.002). (i) Normalized amplitudes of responses were grouped into upper, middle, and lower thirds of the population, and their corresponding decay times averaged (9 cells, 15-36 measurements/category, P<0.002 between categories). (j) Examples of glycinergic IPSCs evoked with one and ten stimuli (10 ms interval). (k) Weighted decay times of the IPSCs against number of stimuli (100 Hz) from five cells. (l) Ten IPSCs delivered at 20 Hz and 200 Hz. (m) Weighted decay times from 7 cells at different frequencies. Comparison of decay times at different frequencies: 20-50 Hz; P<0.01, 50-100 Hz; P<0.05, 100-200 Hz; P < 0.001). Error bars are ±SEM.
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Related In: Results  -  Collection

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Figure 1: Granule cells in the dorsal cochlear nucleus (DCN) and their glycinergic postsynaptic currents(a) Schematic representation of the cochlear nucleus in a coronal brainstem slice, showing the distribution of granule cells (circles) in the DCN and the granule cell region (Grc). (b) Synaptic inputs to granule cells. Granule cells receive excitatory inputs through mossy fibers and the unipolar brush cells (UBC). Inhibitory inputs are assumed to be from the Golgi/stellate neurons. (c) Averaged glycinergic IPSC from a granule cell under control conditions and in 0.5 μM strychnine application. (d) Example traces of glycinergic IPSCs upon synaptic stimulation. Two sample IPSCs of different size are shown in thick and thin black lines. On the right, these IPSCs were normalized and their corresponding weighted decay times are shown. (e) The weighted decay constants of the IPSCs positively correlated with the amplitude. Plot show the values from three cells and their corresponding regression line. The linear fits in the three plots have r=0.92, 0.68 and 0.76 with P<0.0001 for all. (f) IPSC rise times and amplitudes had no correlation. The values from three cells, plotted as rise time and amplitude. Linear fits are insignificant for all cells. (g) Example IPSCs evoked at various voltages. The inset shows the traces normalized, revealing that responses to smaller stimuli decay more quickly. (h) Correlation of amplitude and weighted decay as stimulus strength was changed in four neurons. Correlation coefficients were 0.88, 0.91, 0.93, 0.99 (P<0.002). (i) Normalized amplitudes of responses were grouped into upper, middle, and lower thirds of the population, and their corresponding decay times averaged (9 cells, 15-36 measurements/category, P<0.002 between categories). (j) Examples of glycinergic IPSCs evoked with one and ten stimuli (10 ms interval). (k) Weighted decay times of the IPSCs against number of stimuli (100 Hz) from five cells. (l) Ten IPSCs delivered at 20 Hz and 200 Hz. (m) Weighted decay times from 7 cells at different frequencies. Comparison of decay times at different frequencies: 20-50 Hz; P<0.01, 50-100 Hz; P<0.05, 100-200 Hz; P < 0.001). Error bars are ±SEM.
Mentions: Glycinergic synapses mediate rapid transmission in the brainstem and spinal cord, with typical IPSC decay times of only a few ms 17. Glycine receptors (GlyRs) feature multiple binding sites, and their occupancy has distinctive effects upon gating kinetics 18-20. Well-timed glycinergic inhibition plays a crucial role in determining the synaptic output in several brain regions, particularly in the auditory system, where the precise timing of inhibition is critical to information processing 21. It is generally believed that the decay of glycinergic synaptic currents solely reflects the burst or open duration of GlyR channels 5, 6, 20, 22. The relatively incomplete desensitization exhibited by GlyRs 5, 23 and the slow turnover rates of neurotransmitter transporters 24, 25 suggests the possibility that clearance might determine IPSC decay in some cases. We studied the determinants of glycinergic IPSCs decay in granule cells of the dorsal cochlear nucleus (DCN). The DCN is a laminated structure resembling the cerebellar cortex, in which glycinergic and glutamatergic synaptic activity controls the convergence and plasticity of different sensory streams 26 (Fig 1a,b). DCN granule cells receive strong glycinergic input presumably from Golgi and/or stellate cells 27. In contrast to the rapid decays of most glycinergic IPSCs, typically just a few ms in the adult auditory brainstem 28, 29, glycinergic events last more than 10-times longer in granule cells 27. Varying the frequency and intensity of exocytosis, and interfering with glycine-receptor interactions with a low-affinity competitive antagonist, revealed that transmitter pooling controls the duration of inhibition in an activity-dependent manner.

Bottom Line: We found an exception at glycinergic synapses on granule cells of the rat dorsal cochlear nucleus.These effects could be explained by unique features of GlyRs that are activated by pooling of glycine across synapses.Thus, temporal properties of inhibition can be controlled by activity levels in multiple presynaptic cells or by adjusting release probability at individual synapses.

View Article: PubMed Central - PubMed

Affiliation: Oregon Hearing Research Center, 3181 S.W. Sam Jackson Park Road, Portland, Oregon 97239, USA.

ABSTRACT
Most fast-acting neurotransmitters are rapidly cleared from synaptic regions. This feature isolates synaptic sites, rendering the time course of synaptic responses independent of the number of active synapses. We found an exception at glycinergic synapses on granule cells of the rat dorsal cochlear nucleus. Here the duration of inhibitory postsynaptic currents (IPSCs) was dependent on the number of presynaptic axons that were stimulated and on the number of vesicles that were released from each axon. Increasing the stimulus number or frequency, or blocking glycine uptake, slowed synaptic decays, whereas a low-affinity competitive antagonist of glycine receptors (GlyRs) accelerated IPSC decay. These effects could be explained by unique features of GlyRs that are activated by pooling of glycine across synapses. Functionally, increasing the number of IPSPs markedly lengthened the period of spike inhibition following the cessation of presynaptic stimulation. Thus, temporal properties of inhibition can be controlled by activity levels in multiple presynaptic cells or by adjusting release probability at individual synapses.

Show MeSH
Related in: MedlinePlus