Simultaneous Cellular Imaging, Electrical Recording and Stimulation of Hippocampal Activity in Freely Behaving Mice

Area of Science:

• Neuroscience
• Memory Consolidation Research
• Electrophysiology and Imaging

Background:

• Hippocampal sharp-wave ripples (SWRs) and neural replay are crucial for memory consolidation.
• Electrophysiological methods lack long-term single-neuron tracking for SWR analysis.
• Imaging techniques offer neuron tracking but often lack temporal resolution for SWRs.

Purpose of the Study:

• To develop a dual recording approach combining electrophysiology and calcium imaging for SWR analysis.
• To track individual neuronal contributions to SWRs and neural replay over time.
• To investigate the impact of SWR disruption on neuronal activity patterns.

Main Methods:

• Simultaneous local field potential (LFP) recording in one hippocampal CA1 hemisphere and calcium imaging in the contralateral CA1 of freely behaving mice.
• Custom microdrive array for tetrode implantation and ventral hippocampal commissure (VHC) electrical stimulation for SWR disruption.
• Miniature fluorescent microscope (Miniscope) and genetically encoded calcium indicators for neuronal population imaging.

Main Results:

• Identified a subpopulation of CA1 neurons with synchronous calcium elevation during SWRs.
• Demonstrated that electrical stimulation selectively disrupts SWR-related calcium transients more than non-SWR-related ones.
• Validated the dual recording system's capability to detect and disrupt SWRs.

Conclusions:

• The developed dual recording method enables tracking of individual neuron participation in SWRs and replay.
• This approach overcomes limitations of traditional electrophysiological and imaging techniques.
• Provides a novel tool for studying the dynamic role of neurons in memory consolidation.