TEMPERATURE-DEPENDENT NEURONAL PLASTICITY IN A MOUSE MODEL OF INDUCED HYPOTHERMIA

Torpor is a planned period of lowered physiological activity and metabolism, followed by a large reduction in body temperature. In small-mammals undergoing torpor, synaptic plasticity is reported as rapid and reversible retraction and remodeling of dendrites and spines, followed by an overshoot of synapses in early arousal, when body temperature normalize. Findings of higher amplitude LTP and higher synapse numbers in mice and rats exposed to experimentally induced-torpor-like states, indicate that bouts of hypothermia can induce states of hyperplasticity. In these experiments hypothermia is induced indirectly and secondarily to a planned hypometabolic state, that might contribute to observed plasticity.
Here, we ask if actively inducing deep hypothermia under isoflurane anesthesia by fast cooling, similar to medical hypothermia, could alter synaptic plasticity in mice. To this end, we developed a mouse model of induced deep hypothermia (15 ˙C). Mice awakening from 2 hours of deep hypothermia recover comparably fast to mice awakening from isoflurane anesthesia at normothermia (37 ˙C). Using this experimental paradigm, we show that mice form strong fear memories when conditioned directly after induced deep hypothermia, comparable to untreated animals, but stronger than mice exposed to isoflurane at 37 ˙C. The hightened fear response, compared to the normothermic anaesthetised mice is also reflected in differences in hippocampal CA1 spine morphology between hypothermic and normothermic anesthesized mice. Our results indicate modest temperature-dependent synaptic plasticity under isoflurane anesthesia, but a potential confounding effect of isoflurane anesthesia.