Simultaneous cellular-resolution optical perturbation and imaging of place cell firing fields.
Linking neural microcircuit function to emergent properties of the mammalian brain requires fine-scale manipulation and measurement of neural activity during behavior, where each neuron's coding and dynamics can be characterized. We developed an optical method for simultaneous cellular-resolution stimulation and large-scale recording of neuronal activity in behaving mice. Dual-wavelength two-photon excitation allowed largely independent functional imaging with a green fluorescent calcium sensor (GCaMP3, λ = 920 ± 6 nm) and single-neuron photostimulation with a red-shifted optogenetic probe (C1V1, λ = 1,064 ± 6 nm) in neurons coexpressing the two proteins. We manipulated task-modulated activity in individual hippocampal CA1 place cells during spatial navigation in a virtual reality environment, mimicking natural place-field activity, or 'biasing', to reveal subthreshold dynamics. Notably, manipulating single place-cell activity also affected activity in small groups of other place cells that were active around the same time in the task, suggesting a functional role for local place cell interactions in shaping firing fields.
1] Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey, USA. [2] Bezos Center for Neural Circuit Dynamics, Princeton University, Princeton, New Jersey, USA. [3] Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA. [4] Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA.
John Peter
JP
Rickgauer
1] Department of Bioengineering, Stanford University, Stanford, California, USA. [2] CNC Program, Stanford University, Stanford, California, USA. [3] Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California, USA. [4] Howard Hughes Medical Institute, Stanford University, Stanford, California, USA.
Karl
K
Deisseroth
1] Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey, USA. [2] Bezos Center for Neural Circuit Dynamics, Princeton University, Princeton, New Jersey, USA. [3] Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA. [4] Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA.
David W
DW
Tank
D000818:Animals; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*; D062308:Optogenetics / Q000379:methods*; D010775:Photic Stimulation / Q000379:methods*; D013028:Space Perception / Q000502:physiology*