Retrieval uncertainty drives rapid consolidation of confabulated memories in retrosplenial cortex
- 1Center for Neuroscience, Indian Institute of Science, Bangalore - 560012
Abstract
Learning to make associations in the absence of direct reinforcement, based on previous memories of reward or punishment, is an evolutionary trait quintessential for survival. Little is known about if such higher order associations (HOA) can lead to fabrication of new memories for unreal events. We probed if uncertainty during retrieval of old memory representations can trigger such confabulation. Using chemogenetics, in vivo imaging, and behavior we show that uncertainty in memory perception can not only transfer conditioning to hitherto unexperienced novel context but also can get rapidly consolidated. We find while acquisition of HOA require dorsal-CA1 parvalbumin interneuron activity in intact hippocampus, retrieval requires retrosplenial cortex (RSc). We develop an automated Large-scale Brainwide Correlated Activity Mapping (LaBCAM) method to identify functional connectivity changes across different brain regions in such scenarios. LaBCAM finds that only uncertain remote retrieval engages canonical fear circuitry while regular retrieval does not. Longitudinal imaging of dendritic spines in RSc, a region involved in detection and context-dependent conflict resolution, reveals differential reorganization of spines during acquisition and rapid systems consolidation of HOA. Interestingly, we find HOA is implicated early in AD mice model (APP/PS1) and also in aged animals.
Related
- Related memories exhibit interference during learning in adults but later retrieval in children
- Real-time reorienting during episodic retrieval rescues memories from suboptimal arousal-attentional states
- Organization of retrosplenial cortex projections at the single-neuron level
- Multimodal profiling and intersectional genetics reveal CA1 border inhibitory neuron diversity and postnatal emergence of retrosplenial connectivity
- Subspace communication in the hippocampal–retrosplenial axis
BibTeX
@misc{singh2026retrieval,
title = {{Retrieval uncertainty drives rapid consolidation of confabulated memories in retrosplenial cortex}},
author = {A. Singh and N. Das and P. Ahuja and A. Banerjee and S. Kalvae and A. sane and S. Kundu and S. Rajesh and T. Saha and B. Jayaprakash},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.01.748171},
url = {https://www.biorxiv.org/content/10.64898/2026.09.01.748171v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Retrieval uncertainty drives rapid consolidation of confabulated memories in retrosplenial cortex
AU - A. Singh
AU - N. Das
AU - P. Ahuja
AU - A. Banerjee
AU - S. Kalvae
AU - A. sane
AU - S. Kundu
AU - S. Rajesh
AU - T. Saha
AU - B. Jayaprakash
PY - 2026
DA - 2026/09/01
PB - bioRxiv
DO - 10.64898/2026.09.01.748171
UR - https://www.biorxiv.org/content/10.64898/2026.09.01.748171v1
AB - Learning to make associations in the absence of direct reinforcement, based on previous memories of reward or punishment, is an evolutionary trait quintessential for survival. Little is known about if such higher order associations (HOA) can lead to fabrication of new memories for unreal events. We probed if uncertainty during retrieval of old memory representations can trigger such confabulation. Using chemogenetics, in vivo imaging, and behavior we show that uncertainty in memory perception can not only transfer conditioning to hitherto unexperienced novel context but also can get rapidly consolidated. We find while acquisition of HOA require dorsal-CA1 parvalbumin interneuron activity in intact hippocampus, retrieval requires retrosplenial cortex (RSc). We develop an automated Large-scale Brainwide Correlated Activity Mapping (LaBCAM) method to identify functional connectivity changes across different brain regions in such scenarios. LaBCAM finds that only uncertain remote retrieval engages canonical fear circuitry while regular retrieval does not. Longitudinal imaging of dendritic spines in RSc, a region involved in detection and context-dependent conflict resolution, reveals differential reorganization of spines during acquisition and rapid systems consolidation of HOA. Interestingly, we find HOA is implicated early in AD mice model (APP/PS1) and also in aged animals.
ER -