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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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Burst and tonic spikes occur within exclusive temporal domains.A. The stereotypical response of a TC cell to a 1s, 200 pA depolarising current pulse delivered from resting membrane potential (-65 mV). The onset of the response (first 150 ms, inset) is characterised by a high frequency burst of spikes (246 Hz, arrow) followed by a shift to tonic firing. B . Interspike interval (i.s.i.) histogram (1 ms bin width) from a single TC cell in the response to a set of 20 current steps from 0 to 400 pA. Note the clear segregation either side of the 5 ms interval. Adjacent spikes with intervals shorter than 5 ms were classified as “burst” spikes, while those greater than 5 ms were classified as “tonic” spikes. Intervals greater than 50 ms (4 out of 693 in this example) were excluded from the plot for clarity.
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pone-0057961-g002: Burst and tonic spikes occur within exclusive temporal domains.A. The stereotypical response of a TC cell to a 1s, 200 pA depolarising current pulse delivered from resting membrane potential (-65 mV). The onset of the response (first 150 ms, inset) is characterised by a high frequency burst of spikes (246 Hz, arrow) followed by a shift to tonic firing. B . Interspike interval (i.s.i.) histogram (1 ms bin width) from a single TC cell in the response to a set of 20 current steps from 0 to 400 pA. Note the clear segregation either side of the 5 ms interval. Adjacent spikes with intervals shorter than 5 ms were classified as “burst” spikes, while those greater than 5 ms were classified as “tonic” spikes. Intervals greater than 50 ms (4 out of 693 in this example) were excluded from the plot for clarity.

Mentions: At resting membrane potential all TC cells were silent. In response to a current pulse delivered from rest, TC cells produced action potentials in a stereotypical pattern. Figure 2A shows the typical response of a TC cell to a 1 s current pulse of 200 pA. At the beginning of the current step the cell responded with a burst of high frequency spikes (range: 2–7 spikes/burst, mode: 3 spikes/burst, n  =  28). The magnitude of this burst was independent of injected current; a current pulse sufficient to bring about a LTS led to a burst of spikes that was stable for each neuron. This burst of firing was followed by tonic firing in 24 of the 28 cells, which persisted throughout the current step, and followed the burst by a short latency (65.0 ± 18 ms, n  =  24). Unlike the initial burst response, the frequency of discharge in the tonic period increased with current amplitude (max: 117 Hz), but never approached the rate during burst firing (by definition >200 Hz).


Noise normalizes firing output of mouse lateral geniculate nucleus neurons.

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

Burst and tonic spikes occur within exclusive temporal domains.A. The stereotypical response of a TC cell to a 1s, 200 pA depolarising current pulse delivered from resting membrane potential (-65 mV). The onset of the response (first 150 ms, inset) is characterised by a high frequency burst of spikes (246 Hz, arrow) followed by a shift to tonic firing. B . Interspike interval (i.s.i.) histogram (1 ms bin width) from a single TC cell in the response to a set of 20 current steps from 0 to 400 pA. Note the clear segregation either side of the 5 ms interval. Adjacent spikes with intervals shorter than 5 ms were classified as “burst” spikes, while those greater than 5 ms were classified as “tonic” spikes. Intervals greater than 50 ms (4 out of 693 in this example) were excluded from the plot for clarity.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585224&req=5

pone-0057961-g002: Burst and tonic spikes occur within exclusive temporal domains.A. The stereotypical response of a TC cell to a 1s, 200 pA depolarising current pulse delivered from resting membrane potential (-65 mV). The onset of the response (first 150 ms, inset) is characterised by a high frequency burst of spikes (246 Hz, arrow) followed by a shift to tonic firing. B . Interspike interval (i.s.i.) histogram (1 ms bin width) from a single TC cell in the response to a set of 20 current steps from 0 to 400 pA. Note the clear segregation either side of the 5 ms interval. Adjacent spikes with intervals shorter than 5 ms were classified as “burst” spikes, while those greater than 5 ms were classified as “tonic” spikes. Intervals greater than 50 ms (4 out of 693 in this example) were excluded from the plot for clarity.
Mentions: At resting membrane potential all TC cells were silent. In response to a current pulse delivered from rest, TC cells produced action potentials in a stereotypical pattern. Figure 2A shows the typical response of a TC cell to a 1 s current pulse of 200 pA. At the beginning of the current step the cell responded with a burst of high frequency spikes (range: 2–7 spikes/burst, mode: 3 spikes/burst, n  =  28). The magnitude of this burst was independent of injected current; a current pulse sufficient to bring about a LTS led to a burst of spikes that was stable for each neuron. This burst of firing was followed by tonic firing in 24 of the 28 cells, which persisted throughout the current step, and followed the burst by a short latency (65.0 ± 18 ms, n  =  24). Unlike the initial burst response, the frequency of discharge in the tonic period increased with current amplitude (max: 117 Hz), but never approached the rate during burst firing (by definition >200 Hz).

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