A mouse model of profound hypothermia and rewarming: A system for investigating temperature-dependent synaptic plasticity

During the course of hibernation a rapid and reversible retraction and remodeling of dendrites and spines occurs in the brain of small hibernating mammals. Similar plasticity is also observed in hypothermic mice and rats, suggesting that the phenomenon is not exclusively regulated by hibernation-specific gene expression. While plasticity mechanisms during hibernation have mainly been studied in the hippocampus, the brain wide expression of a reversible and temperature-dependent phosphorylation of microtubule-associated protein tau (MAP-Tau), in both hibernating animals and non-hibernators, further suggests that such plasticity might be found in other brain regions as well.To test the hypothesis that temperature-dependent plasticity in mice can be found outside the hippocampus we exposed mice to hypothermia using deep systemic cooling under general anesthesia and analyzed neuronal morphology post-mortem. For this, we created a minimally invasive cooling paradigm with spontaneous breathing that proved to robustly cool mice of both genders to 15 °C for at least two hours followed by rewarming. To investigate global temperature-dependent plasticity, we labeled neurons sparsely throughout the brain in mice using systemic delivery of AAV-hsyn-cre-PhP.eb:AAV-CAG-TdTomato.Php.eb (0,004:1,v:v). We are comparing neuronal morphology in the hippocampus and the visual cortex of mice that have been exposed to profound hypothermia, anesthesia alone or naïve mice. To further investigate how neuronal activity is influenced by hypothermia, we are recording thousands of neurons in the visual cortex using live 2-photon imaging and soma-targeted Gcamp8.