Limits...
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.

Show MeSH

Related in: MedlinePlus

Contribution of IPSC decay time to the duration of inhibition(a) Example traces showing the duration of inhibition by a single and a train (10 shocks, 100 Hz) of synaptically evoked IPSPs on the granule cell spiking. Black lines at top mark period of the stimuli. Red highlights a single sweep. (b) Traces from panel a are overlaid at time of last stimulus. (c) Period between time of last synaptic stimulus and resumption of action potential firing, for single and trains of IPSPs. The latency before spiking resumed increased significantly following a train of IPSPs (n=8; P < 0.0015). (d) Relation between peak of negative peak of IPSP and latency to spike firing for three cells. Latency increases sharply with larger IPSPs, consistent with longer lasting synaptic conductance. (e) Example traces in which firing was interrupted by negative current steps (marked by brackets) of different amplitude (range −5 to −50 pA) for 10 ms (left sweeps) or 100 ms (right sweeps). (f) Example of overlaid responses at termination of 10 and 100 ms current pulses that hyperpolarized the neuron to a potential near −80 mV. (g) Latency to spike firing after 10- and 100-ms pulses for IPSPs reaching near −80 mV (−75 mV to −82 mV). (h) Relation between most negative point of hyperpolarization and the resulting latency to firing for six cells. These data show a sublinear relation between voltage and latency suggesting a maximal repriming of A-type K+ current. Error bars are ±SEM.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2664096&req=5

Figure 7: Contribution of IPSC decay time to the duration of inhibition(a) Example traces showing the duration of inhibition by a single and a train (10 shocks, 100 Hz) of synaptically evoked IPSPs on the granule cell spiking. Black lines at top mark period of the stimuli. Red highlights a single sweep. (b) Traces from panel a are overlaid at time of last stimulus. (c) Period between time of last synaptic stimulus and resumption of action potential firing, for single and trains of IPSPs. The latency before spiking resumed increased significantly following a train of IPSPs (n=8; P < 0.0015). (d) Relation between peak of negative peak of IPSP and latency to spike firing for three cells. Latency increases sharply with larger IPSPs, consistent with longer lasting synaptic conductance. (e) Example traces in which firing was interrupted by negative current steps (marked by brackets) of different amplitude (range −5 to −50 pA) for 10 ms (left sweeps) or 100 ms (right sweeps). (f) Example of overlaid responses at termination of 10 and 100 ms current pulses that hyperpolarized the neuron to a potential near −80 mV. (g) Latency to spike firing after 10- and 100-ms pulses for IPSPs reaching near −80 mV (−75 mV to −82 mV). (h) Relation between most negative point of hyperpolarization and the resulting latency to firing for six cells. These data show a sublinear relation between voltage and latency suggesting a maximal repriming of A-type K+ current. Error bars are ±SEM.

Mentions: We explored the physiological significance of the variation in decay time by delivering single and repetitive IPSPs and determining how long the IPSPs were able to delay resumption of action potential firing. AMPA, NMDA and GABAA receptor blockers were added to the extracellular solution to isolate glycinergic IPSPs. A continuous depolarizing current injection of 5-10 pA elicited steady action potentials. In response to presynaptic stimuli, IPSPs hyperpolarized the cells and abruptly halted firing (Fig. 7a). Upon a single IPSP, spikes were inhibited for 192±66 ms (latency from stimulus artifact to first spike; n=8). By contrast, upon a train of IPSPs (10 stimuli) the inhibition after the last stimulus was prolonged by over 100 ms (Fig 7a-c; 326±83 ms from last stimulus artifact to resumption of spikes; 91±19% increase; P=0.0015; n=8). While the extent of the delay varied widely among cells (Fig. 7c), the increase in delay was seen in every case, and larger IPSPs tended to produce longer delays (Fig 7d). This effect is not due to recruitment of intrinsic currents by the IPSP, such as A-type K+ currents, as direct hyperpolarizing current injections of different durations produced spike delays of less than 40 ms, much briefer than that seen with IPSPs (Fig 7e-h). Moreover, this difference in decay time between single and train IPSPs is not due to differences in peak synaptic conductance, as demonstrated by examining the duration of spike inhibition with IPSGs of identical duration but different amplitude (Fig S7). Thus, the changes we have observed in the decay of synaptic currents results in comparable changes in the lifetime of inhibition.


Slow glycinergic transmission mediated by transmitter pooling.

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

Contribution of IPSC decay time to the duration of inhibition(a) Example traces showing the duration of inhibition by a single and a train (10 shocks, 100 Hz) of synaptically evoked IPSPs on the granule cell spiking. Black lines at top mark period of the stimuli. Red highlights a single sweep. (b) Traces from panel a are overlaid at time of last stimulus. (c) Period between time of last synaptic stimulus and resumption of action potential firing, for single and trains of IPSPs. The latency before spiking resumed increased significantly following a train of IPSPs (n=8; P < 0.0015). (d) Relation between peak of negative peak of IPSP and latency to spike firing for three cells. Latency increases sharply with larger IPSPs, consistent with longer lasting synaptic conductance. (e) Example traces in which firing was interrupted by negative current steps (marked by brackets) of different amplitude (range −5 to −50 pA) for 10 ms (left sweeps) or 100 ms (right sweeps). (f) Example of overlaid responses at termination of 10 and 100 ms current pulses that hyperpolarized the neuron to a potential near −80 mV. (g) Latency to spike firing after 10- and 100-ms pulses for IPSPs reaching near −80 mV (−75 mV to −82 mV). (h) Relation between most negative point of hyperpolarization and the resulting latency to firing for six cells. These data show a sublinear relation between voltage and latency suggesting a maximal repriming of A-type K+ current. Error bars are ±SEM.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2664096&req=5

Figure 7: Contribution of IPSC decay time to the duration of inhibition(a) Example traces showing the duration of inhibition by a single and a train (10 shocks, 100 Hz) of synaptically evoked IPSPs on the granule cell spiking. Black lines at top mark period of the stimuli. Red highlights a single sweep. (b) Traces from panel a are overlaid at time of last stimulus. (c) Period between time of last synaptic stimulus and resumption of action potential firing, for single and trains of IPSPs. The latency before spiking resumed increased significantly following a train of IPSPs (n=8; P < 0.0015). (d) Relation between peak of negative peak of IPSP and latency to spike firing for three cells. Latency increases sharply with larger IPSPs, consistent with longer lasting synaptic conductance. (e) Example traces in which firing was interrupted by negative current steps (marked by brackets) of different amplitude (range −5 to −50 pA) for 10 ms (left sweeps) or 100 ms (right sweeps). (f) Example of overlaid responses at termination of 10 and 100 ms current pulses that hyperpolarized the neuron to a potential near −80 mV. (g) Latency to spike firing after 10- and 100-ms pulses for IPSPs reaching near −80 mV (−75 mV to −82 mV). (h) Relation between most negative point of hyperpolarization and the resulting latency to firing for six cells. These data show a sublinear relation between voltage and latency suggesting a maximal repriming of A-type K+ current. Error bars are ±SEM.
Mentions: We explored the physiological significance of the variation in decay time by delivering single and repetitive IPSPs and determining how long the IPSPs were able to delay resumption of action potential firing. AMPA, NMDA and GABAA receptor blockers were added to the extracellular solution to isolate glycinergic IPSPs. A continuous depolarizing current injection of 5-10 pA elicited steady action potentials. In response to presynaptic stimuli, IPSPs hyperpolarized the cells and abruptly halted firing (Fig. 7a). Upon a single IPSP, spikes were inhibited for 192±66 ms (latency from stimulus artifact to first spike; n=8). By contrast, upon a train of IPSPs (10 stimuli) the inhibition after the last stimulus was prolonged by over 100 ms (Fig 7a-c; 326±83 ms from last stimulus artifact to resumption of spikes; 91±19% increase; P=0.0015; n=8). While the extent of the delay varied widely among cells (Fig. 7c), the increase in delay was seen in every case, and larger IPSPs tended to produce longer delays (Fig 7d). This effect is not due to recruitment of intrinsic currents by the IPSP, such as A-type K+ currents, as direct hyperpolarizing current injections of different durations produced spike delays of less than 40 ms, much briefer than that seen with IPSPs (Fig 7e-h). Moreover, this difference in decay time between single and train IPSPs is not due to differences in peak synaptic conductance, as demonstrated by examining the duration of spike inhibition with IPSGs of identical duration but different amplitude (Fig S7). Thus, the changes we have observed in the decay of synaptic currents results in comparable changes in the lifetime of inhibition.

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