Hippocampal Engrams Generate Variable Behavioral Responses and Brain-Wide Network States.

Area of Science:

• Neuroscience
• Behavioral Neuroscience
• Systems Neuroscience

Background:

• Freezing is a key defensive behavior studied during hippocampal-dependent fear memory reactivation.
• The precise neural circuits and brain-wide modulations underlying context-dependent freezing remain largely unknown.

Purpose of the Study:

• To investigate how optogenetically reactivated hippocampal fear engrams modulate freezing behavior across different environmental contexts.
• To identify brain-wide network alterations associated with fear engram reactivation and compare them to natural fear memory retrieval.

Main Methods:

• Optogenetic reactivation of a fear engram in the dentate gyrus of male mice across three contexts of varying sizes.
• Graph theoretical analyses of cFos expression to map brain-wide network changes during engram reactivation.
• Comparison of reactivation-induced networks with networks from natural fear memory retrieval.

Main Results:

• Light-induced freezing was context-dependent, being robust in small contexts but absent in large ones.
• Engram reactivation induced positive interregional cFos correlations, forming networks with "fear" and "defense" system hubs.
• Networks from small-context engram reactivation shared modularity and hub characteristics with natural fear memory retrieval networks.

Conclusions:

• Hippocampal fear engram reactivation's influence on freezing is modulated by environmental context size.
• Brain-wide network analysis reveals conserved systems-level mechanisms between artificial engram reactivation and natural memory recall.
• Understanding these circuits offers insights into how memory modulates behavioral states.