Morpho‐physiological properties and connectivity of vasoactive intestinal polypeptide‐expressing interneurons in the mouse hippocampal dentate gyrus

Abstract

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.

Interneuron diversity in the rat dentate gyrus: An unbiased in vitro classification

“…(Eyre & Bartos, 2019;Melzer et al, 2012;Yuan et al, 2017), which possess axons cut during brain slicing. Furthermore, several previously identified IN types were not detected in our study, for example, CCK BCs (Hájos et al, 1996), nor did we assess a full range of neurochemical markers, as such may have overlooked important classifications, such as the various types of VIP/CR INs (Acsády et al, 1996;Hájos et al, 1996;Wei et al, 2021). Additionally, while this study provides a detailed morpho-physiological characterization of 80 INs, greater sampling may elucidate further functional diversity.…”

“…Differences were also apparent in their neuropeptide expression with SP I cells co-expressing NPY and CR together with nNOS in a subset of cells, compared to an exclusive nNOS expression in SP II neurons, indicating their potential molecular heterogeneity. Albeit not tested in the present study, these clusters may also comprise INs expressing vasoactive intestinal peptide (VIP), which have recently been shown as a diverse group in the DG, including atype with axon and dendrites extending into the subiculum(Wei et al, 2021).…”

WNK1 promotes water homeostasis by acting as a central osmolality sensor for arginine vasopressin release

“…Acute brain slices were prepared at least 1 week after the retrograde tracer injection or 3 weeks after the virus injection, and recording was performed as previously described ( 60 ). All animals were sacrificed by decapitation after anesthesia with isoflurane.…”