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Synaptic depression enables neuronal gain control

Nature volume 457, pages 1015–1018 (2009)Cite this article

Abstract

To act as computational devices, neurons must perform mathematical operations as they transform synaptic and modulatory input into output firing rate1. Experiments and theory indicate that neuronal firing typically represents the sum of synaptic inputs1,2,3, an additive operation, but multiplication of inputs is essential for many computations1. Multiplication by a constant produces a change in the slope, or gain, of the input–output relationship, amplifying or scaling down the sensitivity of the neuron to changes in its input. Such gain modulation occurs in vivo, during contrast invariance of orientation tuning4, attentional scaling5, translation-invariant object recognition6, auditory processing7 and coordinate transformations8,9. Moreover, theoretical studies highlight the necessity of gain modulation in several of these tasks9,10,11. Although potential cellular mechanisms for gain modulation have been identified, they often rely on membrane noise and require restrictive conditions to work3,12,13,14,15,16,17,18. Because nonlinear components are used to scale signals in electronics, we examined whether synaptic nonlinearities are involved in neuronal gain modulation. We used synaptic stimulation and the dynamic-clamp technique to investigate gain modulation in granule cells in acute slices of rat cerebellum. Here we show that when excitation is mediated by synapses with short-term depression (STD), neuronal gain is controlled by an inhibitory conductance in a noise-independent manner, allowing driving and modulatory inputs to be multiplied together. The nonlinearity introduced by STD transforms inhibition-mediated additive shifts in the input–output relationship into multiplicative gain changes. When granule cells were driven with bursts of high-frequency mossy fibre input, as observed in vivo19,20, larger inhibition-mediated gain changes were observed, as expected with greater STD. Simulations of synaptic integration in more complex neocortical neurons suggest that STD-based gain modulation can also operate in neurons with large dendritic trees. Our results establish that neurons receiving depressing excitatory inputs can act as powerful multiplicative devices even when integration of postsynaptic conductances is linear.

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Figure 1: Synaptic depression enhances inhibition-mediated gain modulation.
Figure 2: Synaptic depression transforms additive shifts into multiplicative gain modulation.
Figure 3: Gain modulation in the presence of synaptic NMDAR conductances.
Figure 4: Gain modulation during broad bandwidth single mossy fibre stimulation.
Figure 5: Multiplicative gain modulation in a cortical layer 5 pyramidal neuron model.

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Acknowledgements

This was supported by the Wellcome Trust, MRC (G0400598) and EU (EUSynapse, LSHM-CT-2005-019055). R.A.S. is in receipt of a Wellcome Senior Research Fellowship. We thank P. Gleeson for help with neuroConstruct, D. Ward and R. Kanichay for their experimental support, D. Digregorio and P. Kirkby for discussions, and A. Arenz, D. Attwell, G. Billings, E. Chaigneau, D. DiGregorio, M. Farrant, F. Minneci and K. Vervaeke for their comments on the manuscript.

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  1. Laurence Cathala and Volker Steuber: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK,

    Jason S. Rothman, Laurence Cathala, Volker Steuber & R. Angus Silver

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  1. Jason S. Rothman
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Correspondence to R. Angus Silver.

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Rothman, J., Cathala, L., Steuber, V. et al. Synaptic depression enables neuronal gain control. Nature 457, 1015–1018 (2009). https://doi.org/10.1038/nature07604

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