a-c, Simplified diagrams of the hippocampal trisynaptic circuit. Dentate gyrus granule cells (bottom right) project mossy fibers to CA3 pyramidal neurons (left), which project Schaffer collaterals to CA1 pyramidal neurons (top right), which in turn project to extrahippocampal brain regions. A subpopulation of CRH interneurons resides in CA1 stratum pyramidale and back-project to form inhibitory synapses on CA3 pyramidal neurons. a, Under basal physiological conditions, CRH neurons provide minimal inhibitory output to CA3. b, During periods of heightened hippocampal network activity such as active exploration or temporal lobe seizures, CRH neurons are moderately or heavily engaged to inhibit CA3, helping to constrain network excitability within an adaptive range. c, When CRH neurons are removed, the excitability of the network is less constrained, impairing recognition memory and diminishing seizure resistance.