Abstract
The supramammillary nucleus (SuM) provides substantial innervation to the dentate gyrus (DG). It remains unknown how the SuM and DG coordinate their activities at the circuit level to regulate spatial memory. Additionally, SuM co-releases GABA and glutamate to the DG, but the relative role of GABA versus glutamate in regulating spatial memory remains unknown. Here we report that SuM-DG Ca2+ activities are highly correlated during spatial memory retrieval as compared to the moderate correlation during memory encoding when mice are performing a location discrimination task. Supporting this evidence, we demonstrate that the activity of SuM neurons or SuM-DG projections is required for spatial memory retrieval. Furthermore, we show that SuM glutamate transmission is necessary for both spatial memory retrieval and highly-correlated SuM-DG activities during spatial memory retrieval. Our studies identify a long-range SuM-DG circuit linking two highly correlated subcortical regions to regulate spatial memory retrieval through SuM glutamate release.
Highlights
The hippocampus mediates certain forms of learning and memory, such as spatial information processing and pattern separation
Correlation analysis based on frequency spectrums showed that the Ca2+ events from the supramammillary nucleus (SuM) and dentate gyrus (DG) neurons are correlated in the range of 0.1–0.5 Hz (Figure 1—figure supplement 1D–I)
Using an in vivo multi-fiber photometry system to simultaneously record the Ca2+ activities of both the SuM and DG, we provide the first evidence that activities of the SuM and DG become significantly higher and correlated during spatial memory retrieval than those during the encoding phase (Figure 7A)
Summary
The hippocampus mediates certain forms of learning and memory, such as spatial information processing and pattern separation. We focus on the SuM inputs to the DG, based on the dense projections from SuM to DG GCs (Berger et al, 2001; Pedersen et al, 2017; Soussi et al, 2010) Both SuM and DG have been implicated in hippocampal-dependent spatial memory (Ito et al, 2018; Vertes, 2015), but how SuM and DG coordinate their activities during distinct stages of the memory process and regulate this process is unknown. The relative role of GABA versus glutamate released from SuM neurons in regulating the spatial memory process remains to be established. We used the viral-mediated genetic knockdown approach and showed that glutamate (but not GABA) release from SuM is necessary for both spatial memory retrieval and highly correlated SuM-DG Ca2+ activities during spatial memory retrieval
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