Engram reactivation mimics cellular signatures of fear
Rebecca L. Suthard,
Ryan A. Senne,
Michelle D. Buzharsky,
Anh H. Diep,
Angela Y. Pyo,
Steve Ramirez
Affiliations
Rebecca L. Suthard
Graduate Program for Neuroscience, Boston University, Boston, MA 02215, USA; Department of Psychological and Brain Sciences, The Center for Systems Neuroscience, Neurophotonics Center, and Photonics Center, Boston University, Boston, MA 02215, USA
Ryan A. Senne
Graduate Program for Neuroscience, Boston University, Boston, MA 02215, USA; Department of Psychological and Brain Sciences, The Center for Systems Neuroscience, Neurophotonics Center, and Photonics Center, Boston University, Boston, MA 02215, USA
Michelle D. Buzharsky
Department of Psychological and Brain Sciences, The Center for Systems Neuroscience, Neurophotonics Center, and Photonics Center, Boston University, Boston, MA 02215, USA
Anh H. Diep
Department of Psychological and Brain Sciences, The Center for Systems Neuroscience, Neurophotonics Center, and Photonics Center, Boston University, Boston, MA 02215, USA
Angela Y. Pyo
Department of Psychological and Brain Sciences, The Center for Systems Neuroscience, Neurophotonics Center, and Photonics Center, Boston University, Boston, MA 02215, USA
Steve Ramirez
Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA; Department of Psychological and Brain Sciences, The Center for Systems Neuroscience, Neurophotonics Center, and Photonics Center, Boston University, Boston, MA 02215, USA; Corresponding author
Summary: Engrams, or the physical substrate of memory, recruit heterogeneous cell types. Targeted reactivation of neurons processing discrete memories drives the behavioral expression of memory, though the underlying landscape of recruited cells and their real-time responses remain elusive. To understand how artificial stimulation of fear affects intra-hippocampal neuron-astrocyte dynamics as well as their behavioral consequences, we express channelrhodopsin-2 in an activity-dependent manner within dentate gyrus neurons while recording both cell types with fiber photometry in hippocampal ventral CA1 across learning and memory. Both cell types exhibit shock responsiveness, with astrocytic calcium events uniquely modulated by fear conditioning. Optogenetic stimulation of a hippocampus-mediated engram recapitulates coordinated calcium signatures time locked to freezing, mirroring those observed during natural fear memory recall. Our findings reveal cell-type-specific dynamics in the hippocampus during freezing behavior, emphasizing neuronal-astrocytic coupling as a shared mechanism enabling both natural and artificially induced memory retrieval and the behavioral expression of fear.
