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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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TC cells display a wide range of gains and thresholds.A. Firing rate as a function of input current amplitude (f-I relationship) for a typical TC cell. A straight line was fitted from the first point above tonic firing threshold to the last recorded response; the slope of this fit was a measure of gain. The gain and threshold of this neuron were 0.432 Hz/pA and 180 pA respectively. Shown to the right are representative traces recorded in response to 200, 300 and 400 pA (square, diamond, and circle respectively) current pulses. B. Firing threshold plotted as a function of gain. Both measures were normalised against the input resistance of each cell to minimize error associated with cell soma area. The average of each measure (and their respective SEMs) is indicated by the empty circle. A histogram of normalised gain (above) demonstrates that gains are normally distributed.
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pone-0057961-g003: TC cells display a wide range of gains and thresholds.A. Firing rate as a function of input current amplitude (f-I relationship) for a typical TC cell. A straight line was fitted from the first point above tonic firing threshold to the last recorded response; the slope of this fit was a measure of gain. The gain and threshold of this neuron were 0.432 Hz/pA and 180 pA respectively. Shown to the right are representative traces recorded in response to 200, 300 and 400 pA (square, diamond, and circle respectively) current pulses. B. Firing threshold plotted as a function of gain. Both measures were normalised against the input resistance of each cell to minimize error associated with cell soma area. The average of each measure (and their respective SEMs) is indicated by the empty circle. A histogram of normalised gain (above) demonstrates that gains are normally distributed.

Mentions: To analyse changes in the sensitivity of TC cells, we first needed to establish the baseline measures of gain and threshold in the absence of external influences. In the following we restrict our analysis to the tonic component of TC cell spiking activity. We do this because burst spiking provides no graded input-output relationship from which to infer sensitivity, and because the tonic mode represents a more dynamic component of the TC cell firing output. Figure 3A shows the spike frequency vs. current (f-I) relationship in response to current steps for a typical TC cell. In this and all cells, tonic discharge rates rose rapidly and relatively linearly following a threshold, before saturating at a discharge rate of near 100 Hz. The average tonic firing threshold (211 ± 15 pA, n  =  24) was 53% larger than the threshold for burst firing (143 ± 16 pA, n  =  24). We define the tonic threshold as the first current value capable of driving tonic discharge above 3 Hz, and calculated the gain as the slope of a linear fit to the straightest portion of the f-I plot. To allow comparison between cells, the estimated gain and threshold was normalised against input resistance (see Methods). Figure 3B plots these normalised values for the sample of TC cells. Gain was well described by a normal distribution (0.290 ± 0.02 Hz/pA, n  =  24, Fig. 3B; p < 0.01, one-sample Kolmogorov-Smirnov test), while thresholds appeared uniformly distributed. The input sensitivity of TC cells is therefore heterogeneous.


Noise normalizes firing output of mouse lateral geniculate nucleus neurons.

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

TC cells display a wide range of gains and thresholds.A. Firing rate as a function of input current amplitude (f-I relationship) for a typical TC cell. A straight line was fitted from the first point above tonic firing threshold to the last recorded response; the slope of this fit was a measure of gain. The gain and threshold of this neuron were 0.432 Hz/pA and 180 pA respectively. Shown to the right are representative traces recorded in response to 200, 300 and 400 pA (square, diamond, and circle respectively) current pulses. B. Firing threshold plotted as a function of gain. Both measures were normalised against the input resistance of each cell to minimize error associated with cell soma area. The average of each measure (and their respective SEMs) is indicated by the empty circle. A histogram of normalised gain (above) demonstrates that gains are normally distributed.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3585224&req=5

pone-0057961-g003: TC cells display a wide range of gains and thresholds.A. Firing rate as a function of input current amplitude (f-I relationship) for a typical TC cell. A straight line was fitted from the first point above tonic firing threshold to the last recorded response; the slope of this fit was a measure of gain. The gain and threshold of this neuron were 0.432 Hz/pA and 180 pA respectively. Shown to the right are representative traces recorded in response to 200, 300 and 400 pA (square, diamond, and circle respectively) current pulses. B. Firing threshold plotted as a function of gain. Both measures were normalised against the input resistance of each cell to minimize error associated with cell soma area. The average of each measure (and their respective SEMs) is indicated by the empty circle. A histogram of normalised gain (above) demonstrates that gains are normally distributed.
Mentions: To analyse changes in the sensitivity of TC cells, we first needed to establish the baseline measures of gain and threshold in the absence of external influences. In the following we restrict our analysis to the tonic component of TC cell spiking activity. We do this because burst spiking provides no graded input-output relationship from which to infer sensitivity, and because the tonic mode represents a more dynamic component of the TC cell firing output. Figure 3A shows the spike frequency vs. current (f-I) relationship in response to current steps for a typical TC cell. In this and all cells, tonic discharge rates rose rapidly and relatively linearly following a threshold, before saturating at a discharge rate of near 100 Hz. The average tonic firing threshold (211 ± 15 pA, n  =  24) was 53% larger than the threshold for burst firing (143 ± 16 pA, n  =  24). We define the tonic threshold as the first current value capable of driving tonic discharge above 3 Hz, and calculated the gain as the slope of a linear fit to the straightest portion of the f-I plot. To allow comparison between cells, the estimated gain and threshold was normalised against input resistance (see Methods). Figure 3B plots these normalised values for the sample of TC cells. Gain was well described by a normal distribution (0.290 ± 0.02 Hz/pA, n  =  24, Fig. 3B; p < 0.01, one-sample Kolmogorov-Smirnov test), while thresholds appeared uniformly distributed. The input sensitivity of TC cells is therefore heterogeneous.

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