Limits...
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.

Show MeSH

Related in: MedlinePlus

T-type Ca2+ channel block induces additive and multiplicative gain changes.A. Graph plotting the increase in gain during bath-application of 250 µM Ni2+ for each recorded cell. B. As in A., with sAHP plotted for each cell.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3585224&req=5

pone-0057961-g007: T-type Ca2+ channel block induces additive and multiplicative gain changes.A. Graph plotting the increase in gain during bath-application of 250 µM Ni2+ for each recorded cell. B. As in A., with sAHP plotted for each cell.

Mentions: Evidently, changing the spectrum of currents active during the cell’s response can induce significant gain changes. To see which components may be necessary for such changes, we used Ni2+ to block T-type Ca2+ channel mediated currents. In all 4 cells tested, bath application of 250 µM Ni2+ significantly increased gain (Ni2+: 0.50 ± 0.08 Hz/pA, control: 0.25 ± 0.05 Hz/pA, p  =  0.01; Figure 7A) and decreased threshold (Ni2+: 150 ± 25 pA, control: 245 ± 41 pA; p  =  0.03). Interestingly, application of Ni2+ also reduced the sAHP produced by noiseless current steps (Ni2+: 3.1 mV; control: 6.9 mV; n  =  4, p  =  0.03; Figure 7B). Membrane potential (Ni2+: -69.8 mV; control: -67.9 mV; n  =  4, p  =  0.07) and input resistance (Ni2+: 81 MΩ; control: 102 MΩ; n  =  4, p  =  0.1) did not change significantly with the application of nickel. These results suggest that T-type channels may serve to dampen sensitivity in TC neurons not only by increasing the threshold from which tonic action potentials can be fired (the additive component), but also by limiting firing frequency at much higher membrane potentials.


Noise normalizes firing output of mouse lateral geniculate nucleus neurons.

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

T-type Ca2+ channel block induces additive and multiplicative gain changes.A. Graph plotting the increase in gain during bath-application of 250 µM Ni2+ for each recorded cell. B. As in A., with sAHP plotted for each cell.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0057961-g007: T-type Ca2+ channel block induces additive and multiplicative gain changes.A. Graph plotting the increase in gain during bath-application of 250 µM Ni2+ for each recorded cell. B. As in A., with sAHP plotted for each cell.
Mentions: Evidently, changing the spectrum of currents active during the cell’s response can induce significant gain changes. To see which components may be necessary for such changes, we used Ni2+ to block T-type Ca2+ channel mediated currents. In all 4 cells tested, bath application of 250 µM Ni2+ significantly increased gain (Ni2+: 0.50 ± 0.08 Hz/pA, control: 0.25 ± 0.05 Hz/pA, p  =  0.01; Figure 7A) and decreased threshold (Ni2+: 150 ± 25 pA, control: 245 ± 41 pA; p  =  0.03). Interestingly, application of Ni2+ also reduced the sAHP produced by noiseless current steps (Ni2+: 3.1 mV; control: 6.9 mV; n  =  4, p  =  0.03; Figure 7B). Membrane potential (Ni2+: -69.8 mV; control: -67.9 mV; n  =  4, p  =  0.07) and input resistance (Ni2+: 81 MΩ; control: 102 MΩ; n  =  4, p  =  0.1) did not change significantly with the application of nickel. These results suggest that T-type channels may serve to dampen sensitivity in TC neurons not only by increasing the threshold from which tonic action potentials can be fired (the additive component), but also by limiting firing frequency at much higher membrane potentials.

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