Functional imaging of hippocampal place cells at cellular resolution during virtual navigation.
Spatial navigation is often used as a behavioral task in studies of the neuronal circuits that underlie cognition, learning and memory in rodents. The combination of in vivo microscopy with genetically encoded indicators has provided an important new tool for studying neuronal circuits, but has been technically difficult to apply during navigation. Here we describe methods for imaging the activity of neurons in the CA1 region of the hippocampus with subcellular resolution in behaving mice. Neurons that expressed the genetically encoded calcium indicator GCaMP3 were imaged through a chronic hippocampal window. Head-restrained mice performed spatial behaviors in a setup combining a virtual reality system and a custom-built two-photon microscope. We optically identified populations of place cells and determined the correlation between the location of their place fields in the virtual environment and their anatomical location in the local circuit. The combination of virtual reality and high-resolution functional imaging should allow a new generation of studies to investigate neuronal circuit dynamics during behavior.
Dombeck
Daniel A
DA
Department of Molecular Biology and Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey, USA. ddombeck@princeton.edu
Harvey
Christopher D
CD
Tian
Lin
L
Looger
Loren L
LL
Tank
David W
DW
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002540:Cerebral Cortex / Q000502:physiology; D003712:Dendrites / Q000502:physiology; D006624:Hippocampus / Q000166:cytology*; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000145:classification / Q000166:cytology / Q000502:physiology*; D017711:Nonlinear Dynamics; D018408:Patch-Clamp Techniques / Q000379:methods; D013028:Space Perception / Q000502:physiology*; D013037:Spatial Behavior / Q000502:physiology*; D016704:Synapsins / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic / Q000379:methods; D014584:User-Computer Interface
D016704:Synapsins; D002118:Calcium