Supramammillary Nucleus Afferents to the Dentate Gyrus Co-release Glutamate and GABA and Potentiate Granule Cell Output

The supramammillary nucleus (SuM) of the hypothalamus projects to the dentate gyrus (DG) and the CA2 region of the hippocampus. Although the SuM-to-hippocampus circuits have been implicated in spatial and emotional memory formation, little is known about precise neural connections between the SuM and hippocampus. Here, we report that axons of SuM neurons make monosynaptic connections to granule cells (GCs) and GABAergic interneurons, but not to hilar mossy cells, in the DG and co-release glutamate and γ-aminobutyric acid (GABA) at these synapses. Although inputs from the SuM can excite some interneurons, the inputs alone fail to generate spikes in GCs. However, despite the insufficient excitatory drive and GABAergic co-transmission, SuM inputs have net excitatory effects on GCs and can potentiate GC firing when temporally associated with perforant path inputs. Our results indicate that the SuM influences DG information processing by modulating GC outputs. [Display omitted] •SuM neurons make monosynaptic connections to GCs and GABAergic neurons in the DG•SuM afferents co-release glutamate and GABA to both GCs and GABAergic neurons•SuM inputs can facilitate GC firing when associated with perforant path inputs•SuM inputs have net excitatory effects on GCs and modulate outputs from the DG The supramammillary nucleus (SuM)-to-hippocampus network is implicated in spatial and emotional memory formation, but little is known about precise neural connections. Hashimotodani et al. show that SuM afferents to the dentate gyrus co-release glutamate and GABA, evoke monosynaptic responses in granule cells (GCs) and GABAergic interneurons, and facilitate GC output.