Forsøksdyr: Population codes for learning and memory in the mouse hippocampal formation

Godkjenningsdato 16.05.2018

Godkjenningsperiode 16.05.2018-15.05.2022

Much is known about the neural basis of learning and memory from electrophysiological recordings of rodent neurons on the one hand, and neuroimaging studies of neural populations in humans on the other. Yet, the link between discoveries made in rodents and humans using cellular recordings and macroscopic neuroimaging, respectively, remains unclear. To close this knowledge gap, this application covers the use of mice (mus musculus, n=119) for experiments utilizing a neuroimaging method called functional calcium imaging, which will allow us to record large populations of cells in animals as they perform learning and memory tasks. We will image brain regions known to be involved in learning and memory, including the hippocampus and entorhinal cortex. Two types of behavioral tasks will be utilized, including a traditional spatial memory task and a novel conceptual learning task. The work described in this application is for rodent research only; however, we are also conducting analogous neuroimaging research with humans, and will compare these animal research findings directly with those in humans. Our hope is that this work will ultimately improve translation of findings from animal models of disease to humans, especially for those diseases that impair learning and memory in the hippocampal formation such as Alzheimer’s disease.

The well-being and health of the animals used in these experiments will be continuously monitored, and they are not expected to experience pain or distress during the experiments. Surgery will be conducted using a strict anesthesia and analgesia regime that will eliminate distress during surgery, and careful post-operative care will be used to ensure that animals experience minimal discomfort. Since the behavioral tasks used in these experiments involve awake, behaving animals, the experiments cannot be conducted in vitro. Moreover, they cannot be conducted in invertebrates because they are lacking the brain structures of interest. To reduce the number of animals needed to a minimum, we will perform behavioral pilot experiments and optimize our surgery techniques. Through the perfection of surgery technique and limitation of the duration and number of surgeries, severity of the experiments will be reduced. Severity will be further reduced by habituating the animals to the behavioral tasks so as to reduce the stress-levels.