A contextual fear conditioning paradigm in head-fixed mice exploring virtual reality.

Area of Science:

• Neuroscience
• Behavioral Neuroscience
• Cognitive Neuroscience

Background:

• Contextual fear conditioning (CFC) is a key paradigm for studying associative memory.
• Advanced techniques like multi-photon microscopy require head-fixed animals, limiting CFC studies.
• Existing CFC paradigms for head-fixed mice lack freezing as a behavioral readout.

Purpose of the Study:

• To develop a novel CFC paradigm for head-fixed mice utilizing virtual reality (VR).
• To enable the use of freezing behavior as a measure of fear in head-fixed mice during CFC.
• To investigate the neural underpinnings of fear memory formation and recall using advanced imaging.

Main Methods:

• Developed a VR apparatus for head-fixed mice to undergo CFC with tail shock delivery.
• Tested three variations of the VR CFC paradigm.
• Utilized two-photon calcium imaging to monitor hippocampal CA1 neuronal activity.

Main Results:

• Head-fixed mice exhibited context-specific freezing behavior in the VR environment.
• Freezing responses were significantly increased in the shock-paired VR environment compared to a neutral one.
• Hippocampal CA1 place cells showed remapping and field narrowing post-fear conditioning, similar to freely moving mice.

Conclusions:

• The developed VR CFC paradigm is effective for head-fixed mice, enabling fear conditioning and context-specific freezing.
• This paradigm facilitates the integration of advanced neuroimaging techniques with CFC.
• It opens new avenues for researching the neural mechanisms of fear memory formation, recall, and extinction.