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Noise normalizes firing output of mouse lateral geniculate nucleus neurons.

Wijesinghe R, Solomon SG, Camp AJ - PLoS ONE (2013)

Bottom Line: As expected, injection of current noise via the recording pipette induces shifts in neuronal gain that are dependent on the amplitude of current noise, such that larger shifts in gain are observed in response to larger amplitude noise injections.In contrast, when the cortical feedback network was activated, only multiplicative gain changes were observed.These network activation-dependent changes were associated with reductions in the slow afterhyperpolarization (sAHP), and were mediated at least in part, by T-type calcium channels.

View Article: PubMed Central - PubMed

Affiliation: Sydney Medical School, School of Medical Sciences and Bosch Institute, The University of Sydney, New South Wales, Australia.

ABSTRACT
The output of individual neurons is dependent on both synaptic and intrinsic membrane properties. While it is clear that the response of an individual neuron can be facilitated or inhibited based on the summation of its constituent synaptic inputs, it is not clear whether subthreshold activity, (e.g. synaptic "noise"--fluctuations that do not change the mean membrane potential) also serve a function in the control of neuronal output. Here we studied this by making whole-cell patch-clamp recordings from 29 mouse thalamocortical relay (TC) neurons. For each neuron we measured neuronal gain in response to either injection of current noise, or activation of the metabotropic glutamate receptor-mediated cortical feedback network (synaptic noise). As expected, injection of current noise via the recording pipette induces shifts in neuronal gain that are dependent on the amplitude of current noise, such that larger shifts in gain are observed in response to larger amplitude noise injections. Importantly we show that shifts in neuronal gain are also dependent on the intrinsic sensitivity of the neuron tested, such that the gain of intrinsically sensitive neurons is attenuated divisively in response to current noise, while the gain of insensitive neurons is facilitated multiplicatively by injection of current noise- effectively normalizing the output of the dLGN as a whole. In contrast, when the cortical feedback network was activated, only multiplicative gain changes were observed. These network activation-dependent changes were associated with reductions in the slow afterhyperpolarization (sAHP), and were mediated at least in part, by T-type calcium channels. Together, this suggests that TC neurons have the machinery necessary to compute multiple output solutions to a given set of stimuli depending on the current level of network stimulation.

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Increased synaptic noise induces multiplicative gain changes.A and B. Bath-application of 250 µM trans-ACPD increased the standard deviation of the membrane potential in TC cells. Note the large increase in activity centred around baseline (dashed line, -67 mV) in A. The increase in SD is comparable to the highest level of current noise (1.57 vs 1.6 ). C. For each individual cell (n  =  3) bath application of trans-ACPD increased gain in comparison to control. The increase in gain was paralleled by a reduction in the amplitude of the sAHP (D; main panel and inset).
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pone-0057961-g006: Increased synaptic noise induces multiplicative gain changes.A and B. Bath-application of 250 µM trans-ACPD increased the standard deviation of the membrane potential in TC cells. Note the large increase in activity centred around baseline (dashed line, -67 mV) in A. The increase in SD is comparable to the highest level of current noise (1.57 vs 1.6 ). C. For each individual cell (n  =  3) bath application of trans-ACPD increased gain in comparison to control. The increase in gain was paralleled by a reduction in the amplitude of the sAHP (D; main panel and inset).

Mentions: Excitatory corticothalamic synapses, mediated by postsynaptic mGluR1a glutamate receptors [11], account for about 30% of the total synaptic input onto TC cells in dLGN [20], [34]. These corticothalamic synapses may act as a potent source of synaptic noise, and thereby modulate the input sensitivity of TC cells. To test this hypothesis, we bath-applied the mGluR1a agonist trans-ACPD [35]. In 7 cells tested, bath-application of trans-ACPD significantly depolarised the membrane (trans-ACPD: -62.9 ± 4.5 mV; control: -66.8 ± 4.6 mV; n  =  7, p < 0.005), increased the standard deviation of the membrane potential (trans-ACPD: 1.6 ± 0.34 mV; control: 0.72 ± 0.21 mV; n  =  7, p < 0.01; Figures 6A & B). The SD of the membrane potential during trans-ACPD application approximated that produced by the highest level of current noise (1.57 mV). To determine whether pharmacologically induced synaptic activity would induce gain changes similar to those seen with noisy current stimuli, we delivered noiseless current pulses to 3 cells during the application of trans-ACPD. Gain significantly increased in each of these cells (trans-ACPD: 0.39 ± 0.12 Hz/pA; control: 0.25 ± 0.13 Hz/pA; n  =  3, p  =  0.03, Fig. 6C), while threshold tended to decrease (trans-ACPD: 187 ± 87 pA; control: 293 ± 59 pA; n  =  3, p  =  0.11), along with the input resistance (trans-ACPD: 27 MΩ; control: 53 MΩ; n  =  3, p  =  0.11). Unlike the case with simulated current noise, trans-ACPD always produced an increase in gain in the recorded cell, regardless of the initial gain.


Noise normalizes firing output of mouse lateral geniculate nucleus neurons.

Wijesinghe R, Solomon SG, Camp AJ - PLoS ONE (2013)

Increased synaptic noise induces multiplicative gain changes.A and B. Bath-application of 250 µM trans-ACPD increased the standard deviation of the membrane potential in TC cells. Note the large increase in activity centred around baseline (dashed line, -67 mV) in A. The increase in SD is comparable to the highest level of current noise (1.57 vs 1.6 ). C. For each individual cell (n  =  3) bath application of trans-ACPD increased gain in comparison to control. The increase in gain was paralleled by a reduction in the amplitude of the sAHP (D; main panel and inset).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3585224&req=5

pone-0057961-g006: Increased synaptic noise induces multiplicative gain changes.A and B. Bath-application of 250 µM trans-ACPD increased the standard deviation of the membrane potential in TC cells. Note the large increase in activity centred around baseline (dashed line, -67 mV) in A. The increase in SD is comparable to the highest level of current noise (1.57 vs 1.6 ). C. For each individual cell (n  =  3) bath application of trans-ACPD increased gain in comparison to control. The increase in gain was paralleled by a reduction in the amplitude of the sAHP (D; main panel and inset).
Mentions: Excitatory corticothalamic synapses, mediated by postsynaptic mGluR1a glutamate receptors [11], account for about 30% of the total synaptic input onto TC cells in dLGN [20], [34]. These corticothalamic synapses may act as a potent source of synaptic noise, and thereby modulate the input sensitivity of TC cells. To test this hypothesis, we bath-applied the mGluR1a agonist trans-ACPD [35]. In 7 cells tested, bath-application of trans-ACPD significantly depolarised the membrane (trans-ACPD: -62.9 ± 4.5 mV; control: -66.8 ± 4.6 mV; n  =  7, p < 0.005), increased the standard deviation of the membrane potential (trans-ACPD: 1.6 ± 0.34 mV; control: 0.72 ± 0.21 mV; n  =  7, p < 0.01; Figures 6A & B). The SD of the membrane potential during trans-ACPD application approximated that produced by the highest level of current noise (1.57 mV). To determine whether pharmacologically induced synaptic activity would induce gain changes similar to those seen with noisy current stimuli, we delivered noiseless current pulses to 3 cells during the application of trans-ACPD. Gain significantly increased in each of these cells (trans-ACPD: 0.39 ± 0.12 Hz/pA; control: 0.25 ± 0.13 Hz/pA; n  =  3, p  =  0.03, Fig. 6C), while threshold tended to decrease (trans-ACPD: 187 ± 87 pA; control: 293 ± 59 pA; n  =  3, p  =  0.11), along with the input resistance (trans-ACPD: 27 MΩ; control: 53 MΩ; n  =  3, p  =  0.11). Unlike the case with simulated current noise, trans-ACPD always produced an increase in gain in the recorded cell, regardless of the initial gain.

Bottom Line: As expected, injection of current noise via the recording pipette induces shifts in neuronal gain that are dependent on the amplitude of current noise, such that larger shifts in gain are observed in response to larger amplitude noise injections.In contrast, when the cortical feedback network was activated, only multiplicative gain changes were observed.These network activation-dependent changes were associated with reductions in the slow afterhyperpolarization (sAHP), and were mediated at least in part, by T-type calcium channels.

View Article: PubMed Central - PubMed

Affiliation: Sydney Medical School, School of Medical Sciences and Bosch Institute, The University of Sydney, New South Wales, Australia.

ABSTRACT
The output of individual neurons is dependent on both synaptic and intrinsic membrane properties. While it is clear that the response of an individual neuron can be facilitated or inhibited based on the summation of its constituent synaptic inputs, it is not clear whether subthreshold activity, (e.g. synaptic "noise"--fluctuations that do not change the mean membrane potential) also serve a function in the control of neuronal output. Here we studied this by making whole-cell patch-clamp recordings from 29 mouse thalamocortical relay (TC) neurons. For each neuron we measured neuronal gain in response to either injection of current noise, or activation of the metabotropic glutamate receptor-mediated cortical feedback network (synaptic noise). As expected, injection of current noise via the recording pipette induces shifts in neuronal gain that are dependent on the amplitude of current noise, such that larger shifts in gain are observed in response to larger amplitude noise injections. Importantly we show that shifts in neuronal gain are also dependent on the intrinsic sensitivity of the neuron tested, such that the gain of intrinsically sensitive neurons is attenuated divisively in response to current noise, while the gain of insensitive neurons is facilitated multiplicatively by injection of current noise- effectively normalizing the output of the dLGN as a whole. In contrast, when the cortical feedback network was activated, only multiplicative gain changes were observed. These network activation-dependent changes were associated with reductions in the slow afterhyperpolarization (sAHP), and were mediated at least in part, by T-type calcium channels. Together, this suggests that TC neurons have the machinery necessary to compute multiple output solutions to a given set of stimuli depending on the current level of network stimulation.

Show MeSH
Related in: MedlinePlus