Overview

In conventional electrophysiological recording, cellular properties can be characterized in detail for a single cell and cellular interactions can be studied among at most two or three cells. Functional imaging, on the other hand, provides the ability to characterize dynamic properties of multiple cells (>1000 cells) simultaneously. Activity can be monitored in individual hippocampal subregions and/or the entire hippocampal circuit. The results obtained from various functional imaging approaches have the potential to be tremendously informative. However, dynamic imaging of neuronal circuit function is challenging, with achievement of the necessary spatial and temporal resolution required to resolve neuronal responses constituting the most difficult aspect of optical recording. Neurons and their processes are small, with a spatial extent measured in micrometers. In contrast, the circuits within which neurons function may extend millimeters to a centimeter or more. Studies examining circuit function must retain cellular resolution, while probing areas spanning regions orders of magnitude larger in size. This difficulty in spatial resolution is additionally compounded by the demanding temporal requirements of circuit recordings. The fundamental neuronal activities are action potential (AP) firing and synaptic transmission, with an AP lasting 0.5-2 milliseconds and a synaptic response lasting 10-50 milliseconds in duration. To capture these events, any imaging method should have a temporal resolution of 1 kHz or better. To date, no single microscopic imaging approach can fulfill the requirements. However, integration of a combination of multiple imaging approaches can begin to accomplish this goal.