The dentate gyrus (DG) is the primary gate of the hippocampus and controls
information flow from the cortex to the hippocampus proper. To maintain normal
function, granule cells (GCs), the principal neurons in the DG, receive fine-
tuned inhibition from local-circuit GABAergic inhibitory interneurons (INs).
Abnormalities of GABAergic circuits in the DG are associated with several
brain disorders, including epilepsy, autism, schizophrenia, and Alzheimer
disease. Therefore, understanding the network mechanisms of inhibitory control
of GCs is of functional and pathophysiological importance. GABAergic
inhibitory INs are heterogeneous, but it is unclear how individual subtypes
contribute to GC activity. Using cell-type-specific optogenetic perturbation,
we investigated whether and how two major IN populations defined by
parvalbumin (PV) and somatostatin (SST) expression, regulate GC input
transformations. We showed that PV-expressing (PV+) INs, and not SST-
expressing (SST+) INs, primarily suppress GC responses to single cortical
stimulation. In addition, these two IN classes differentially regulate GC
responses to θ and γ frequency inputs from the cortex. Notably, PV+ INs
specifically control the onset of the spike series, whereas SST+ INs
preferentially regulate the later spikes in the series. Together, PV+ and SST+
GABAergic INs engage differentially in GC input-output transformations in
response to various activity patterns
