Complementary modulation of somatic inhibition by opioids and cannabinoids.

Somatic inhibition, which is critical for determining the spike output of principal cells, is mediated by two physiologically distinct classes of GABAergic interneurons called basket cells. In the hippocampus, despite both targeting the somatic membrane of CA1 pyramidal cells, these two classes of basket cells are active at different times. Differential modulation of these two types of basket cells could hence be important for regulating the activity patterns of CA1 pyramidal cells at very specific periods during ongoing activity. Indeed, cannabinoids selectively suppress the output of one class of basket cell. Whether opioids, another major modulator of inhibition in the hippocampus, also selectively suppress somatic inhibition is not known. Here, we show that basket cells are selectively modulated by either opioids or cannabinoids, but not both. We also find that basket cells are integrated into specific inhibitory subnetworks that are themselves under differential control of opioids and cannabinoids. Furthermore, because the two interneuron types are activated at different times, opioids and cannabinoids suppress different epochs of inhibition. This cell-type specific sensitivity to neuromodulators allows for a fine control of the temporal structure of hippocampal activity.