Synaptic inhibition shapes the response properties of nearly every neuron in the auditory cortex (AC), either directly (through synaptic inhibition onto the examined neuron) or indirectly (by inhibiting the cells that synapse onto it). Within the AC, the numerous subtypes of inhibitory interneurons show a remarkable diversity in their anatomical, electrical, and molecular properties. Much effort has been expended to relate interneuron types and their specializations to their specific computational roles. One common, conceptually straightforward framework models the effects of synaptic inhibition as a linear transformation with a divisive (scaling) and a subtractive (shifting) component. In this view, the essential question is whether the suppression that an interneuron type provides is predominantly divisive or predominantly subtractive.

We evaluated the extent to which activating somatostatin- and parvalbumin-positive interneurons subtractively or divisively suppressed auditory cortical cells' responses to tones. We found that activating either family of interneuron produced mixtures of divisive and subtractive effects, and that simultaneously recorded neurons were often suppressed in qualitatively different ways. Both phenomena occurred in awake, as well as anesthetized, animals.

To explain these observations, we used a simple network model to show that threshold nonlinearities can interact with network activity to transform subtractive inhibition of neurons into divisive inhibition of networks, or vice versa. Varying just two properties of a model neuron (its threshold and the overall strength of suppression) could determine whether the apparent linear effect of inhibition appeared divisive, subtractive, or both. We conclude that the characteristics of response inhibition specific to a single interneuron type can be "masked" by the network configuration and cellular properties of the network in which they are embedded. Through this mechanism, inhibitory interneurons can implement network-level suppression that is qualitatively different from that induced in individual targets, allowing for diverse effects on information processing in different cells.