Morpho-physiological properties and connectivity of vasoactive intestinal polypeptide-expressing interneurons in the...

The hippocampus is a key brain structure for cognitive and emotional functions. Among the hippocampal subregions, the dentate gyrus (DG) is the first station that receives multimodal sensory information from the cortex. Local-circuit inhibitory GABAergic interneurons (INs) regulate the excitation-inhibition balance in the DG principal neurons (PNs) and therefore are critical for information processing. Similar to PNs, GABAergic INs also receive distinct inhibitory inputs. Among various classes of INs, vasoactive intestinal polypeptide-expressing (VIP⁺ ) INs preferentially target other INs in several brain regions and thereby directly modulate the GABAergic system. However, the morpho-physiological characteristics and postsynaptic targets of VIP⁺ INs in the DG are poorly understood. Here, we report that VIP⁺ INs in the mouse DG are highly heterogeneous based on their morpho-physiological characteristics. In approximately two-thirds of morphologically reconstructed cells, their axons ramify in the hilus. The remaining cells project their axons exclusively to the molecular layer (15%), to both the molecular layer and hilus (10%), or throughout the entire DG layers (8%). Generally, VIP⁺ INs display variable intrinsic properties and discharge patterns without clear correlation with their morphologies. Finally, VIP⁺ INs are recruited with a long latency in response to theta-band cortical inputs and preferentially innervate GABAergic INs over glutamatergic PNs. In summary, VIP⁺ INs in the DG are composed of highly diverse subpopulations and control the DG output via disinhibition.