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Balanced inhibition underlies tuning and sharpens spike timing in auditory cortex

Abstract

Neurons in the primary auditory cortex are tuned to the intensity and specific frequencies of sounds, but the synaptic mechanisms underlying this tuning remain uncertain. Inhibition seems to have a functional role in the formation of cortical receptive fields, because stimuli often suppress similar or neighbouring responses1,2,3, and pharmacological blockade of inhibition broadens tuning curves4,5. Here we use whole-cell recordings in vivo to disentangle the roles of excitatory and inhibitory activity in the tone-evoked responses of single neurons in the auditory cortex. The excitatory and inhibitory receptive fields cover almost exactly the same areas, in contrast to the predictions of classical lateral inhibition models. Thus, although inhibition is typically as strong as excitation, it is not necessary to establish tuning, even in the receptive field surround. However, inhibition and excitation occurred in a precise and stereotyped temporal sequence: an initial barrage of excitatory input was rapidly quenched by inhibition, truncating the spiking response within a few (1–4) milliseconds. Balanced inhibition might thus serve to increase the temporal precision6 and thereby reduce the randomness of cortical operation, rather than to increase noise as has been proposed previously7.

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Figure 1: Tones evoked large transient excitatory and inhibitory conductances of comparable magnitudes.
Figure 2: Excitatory, inhibitory, and total synaptic conductances were co-tuned for sound frequency and intensity.
Figure 3: Co-tuned excitation and inhibition governs spiking.
Figure 4: Excitatory conductance preceded inhibitory conductance by a brief delay.
Figure 5: Simulation showing that excitation followed by balanced inhibition increases temporal precision, whereas excitation balanced on average by inhibition decreases temporal precision, using an integrate-and-fire model.

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Acknowledgements

We thank K. Miller, L. Miller, M. Kvale, Z. Mainen, M. DeWeese and M. Sutter for comments on an earlier version of this manuscript. This work has been supported by grants to A.M.Z. from the Packard Foundation, the Sloan Foundation, the NIH and the Mathers Foundation.

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Correspondence to Anthony M. Zador.

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Wehr, M., Zador, A. Balanced inhibition underlies tuning and sharpens spike timing in auditory cortex. Nature 426, 442–446 (2003). https://doi.org/10.1038/nature02116

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