Reconfiguration of the cortical-hippocampal interaction may compensate for Sharp-Wave Ripple deficits in APP/PS1 mice...

Area of Science:

• Neuroscience
• Systems Neuroscience
• Cognitive Neuroscience

Background:

• Alzheimer's disease (AD) impairs memory formation, yet network-level interactions underlying these deficits remain unclear.
• Hippocampal-cortical dialogue, crucial for spatial memory consolidation, involves hippocampal ripple oscillations (SWRs).
• APP/PS1 mice, an AD model, can learn spatial tasks despite deficits in SWRs, suggesting compensatory mechanisms.

Purpose of the Study:

• To investigate network-level hippocampal-cortical interactions during spatial memory consolidation in an AD mouse model.
• To identify causal relationships between hippocampal and cortical circuits during SWRs in APP/PS1 mice compared to wild-type controls.

Main Methods:

• Analysis of multielectrode intracranial recordings from APP/PS1 and wild-type mice during spatial memory consolidation.
• Application of Directed Transfer Function (DTF), a Granger causality-based measure, to assess effective coupling between brain regions.
• Examination of oscillatory activity in ripple (130-180 Hz) and slow gamma (20-60 Hz) frequency bands during SWRs.

Main Results:

• Hippocampal-cortical coupling during SWRs occurred in ripple and slow gamma bands in both groups.
• APP/PS1 mice showed stronger and more widespread slow gamma coupling than wild-type mice.
• Cortico-hippocampal coupling in the ripple band shifted from posterior cortical areas (wild-type) to anterior areas (APP/PS1 mice).

Conclusions:

• Spatial memory consolidation in an AD mouse model involves a reconfiguration of hippocampal-cortical dialogue.
• Altered connectivity patterns, particularly in the slow gamma band and anterior cortical interactions, may represent an adaptive mechanism.
• These findings highlight network-level adaptations in response to AD-related SWR deficits during memory consolidation.