Presynaptic kainate receptors onto somatostatin interneurons are recruited by activity throughout development and contribute to cortical sensory adaptation.

Somatostatin (SST) interneurons produce delayed inhibition due to the short-term facilitation of their excitatory inputs created by the expression of metabotropic glutamate receptor 7 (mGluR7) and presynaptic GluK2-containing kainate receptors (GluK2-KARs). Using mice of both sexes, we find that as synaptic facilitation at L2/3 SST cell inputs increases during the first few postnatal weeks, so does GluK2-KAR expression. Removal of sensory input by whisker trimming does not affect mGluR7, but prevents the emergence of presynaptic GluK2-KARs, which can be restored by allowing whisker regrowth or by acute calmodulin activation. Conversely, late trimming or acute inhibition of CaMKII is sufficient to reduce GluK2-KAR activity. This developmental and activity-dependent regulation also produces a specific reduction of L4 GluK2-KARs that advances in parallel with the maturation of sensory processing in L2/3. Finally, we find that removal of both GluK2-KARs and mGluR7 from the synapse eliminates short-term facilitation and reduces sensory adaptation to repetitive stimuli, first in L4 of somatosensory cortex, then later in development in L2/3.Excitatory synapses onto somatostatin (SOM) interneurons express presynaptic, calcium permeable kainate receptors containing the GluK2 subunit (GluK2-KARs), activated by high frequency activity. In this study we find that their presence onto L2/3 SOM synapses in the barrel cortex is not based on a hardwired genetic program, but instead is regulated by sensory activity, in contrast to that of metabotropic glutamate receptor 7 (mGluR7). Thus, in addition to standard synaptic potentiation and depression mechanisms, excitatory synapses onto SOM neurons undergo an activity-dependent presynaptic modulation that employs GluK2-KARs. Further, we present evidence that loss of the frequency dependent synaptic components (both GluK2-KARs and mGluR7 via Elfn1 deletion) contributes to a decrease in the sensory adaptation commonly seen upon repetitive stimulus presentation.