But wait there’s more! We can turn these cells on, but can we also turn them off?

By using engram specific DREADDs, if we inhibit the DG engram cells, we see no increases in whole-body metabolism.

By labelling neurons in the DG at 4°C, we can later activate them with light at the flick of a switch.🎚️🔋⚡️

Through activating the DG engram cells we find:

📈Whole-body metabolism
📈BAT thermogenesis genes
📈Engrams in the LHA, suggesting connectivity with the DG.

We can visualise the cells that are important for the cold memory in the DG and LHA.

We show that only the mice that reexperience the previous 4oC environment show increased cell overlap (🟢+🔴=🟡) -> meaning the cells active during the cold, are also active during the memory.

Therefore, the memory of a cold environment alone, can increase whole-body metabolism when not in the cold. 🐭💭❄️

What pathways mediate the cold memory brain-body connection? We found increased coordinated activity between the HPC and HY, particularly the DG and LHA.

We found that mice who have previously experienced a cold (4oC) environment will:

📈Increase their whole-body metabolism🔥, and
📈Upregulate heat producing genes in brown fat to stay warm. 🔥

In response to the previously 4oC environment – but in the ABSENCE of the cold (21oC).