Imaging neural activity during spatial learning

Learning requires the brain to store information. Changes in the strength of signalling between individual synapses alters the strength of neuronal connectivity and in turn leads to persistent changes in their firing patterns. The hippocampus is important for encoding information about our spatial location within our environment. Place cells exist within the hippocampus which fire in response to a particular spatial position. These cells use information acquired from the environment to update an animal about its location. Pyramidal cells within superficial and deep layers of the hippocampus sub serve different purposes. Those that are in deeper layers update their activity in response to goal-oriented tasks whereas those in superficial layers hold a more permanent representation of space. This separation of function allows animals to learn new information about an environment whilst preserving a stable copy of the environment itself.
We have developed a state-of-the-art, miniature microscope that is small and light enough to be attached to a mouse's head and which allows imaging in freely moving animals, overcoming the methodological limitations of imaging in head-fixed rodents. Using fluorescent protein calcium sensors that can be targeted to specific regions within the hippocampus, we will record the neuronal activity of large numbers of pyramidal cells within different regions of the hippocampus to record place cell activity in freely moving animals within an environment whilst they are learning a series of behavioural tasks which are dependent upon hippocampal function. We have previously shown that aging results in an increase in presynaptic calcium within the CA1 region of the hippocampus. We will examine how neural activity changes with age and examine whether pharmacological interventions designed to lower presynaptic calcium can reverse the neural, cognitive and behavioural changes associated with aging.