Voltage Imaging in the Study of Hippocampal Circuit Function and Plasticity

Synaptic plasticity has the capacity to alter the function of neural circuits, and long-term potentiation (LTP) of synaptic transmission induced by high frequency electrical activity has the capacity to store information in neural circuits. The cellular and molecular mechanisms of LTP have been studied intensively for many years and much progress has been made on this front. By contrast, how synaptic plasticity alters circuit function has received much less attention and remains poorly understood. Voltage imaging provides a powerful general technique for the study of neural circuitry, and studies of synaptic plasticity with voltage imaging are beginning to reveal important aspects of how the function of a neural circuit can change when the strength of its synapses has been modified. The hippocampus has an important role in learning and memory and the plasticity of its synapses has received much attention. Voltage imaging with voltage sensitive dye in the CA1 region of a hippocampal slice has shown that spatial patterns of enhancement following LTP induction can diverge from the spatial patterns elicited by electrical stimulation, suggesting that LTP exhibits a distinct organizational structure. LTP can alter the throughput of electrical activity in the dentate gyrus of a hippocampal slice, to gate transmission on to the CA3 region. The spatial patterns evoked by complex electrical stimulation can be stored within the CA3 region in a hippocampal slice, allowing patterns to be reconstructed with simpler electrical stimulation. Thus, voltage imaging has demonstrated that the CA3 circuit has the capacity for pattern completion. These studies with voltage sensitive dye illustrate a range of interesting and novel questions that can be addressed at the population level. It is hoped that future imaging experiments with single-cell resolution using genetically-encoded voltage sensors will provide a more detailed picture of how synaptic plasticity modifies the information processing capabilities of neural circuits.