A dentate gyrus- CA3 inhibitory circuit promotes evolution of hippocampal-cortical ensembles during memory consolidation

Abstract
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Abstract

Memories encoded in the dentate gyrus (DG) - CA3 circuit of the hippocampus are routed from CA1 to anterior cingulate cortex (ACC) for consolidation. Although CA1 parvalbumin inhibitory neurons (PV INs) orchestrate hippocampal-cortical communication, we know less about CA3 PV INs or DG - CA3 principal neuron - IN circuit mechanisms that contribute to evolution of hippocampal-cortical ensembles during memory consolidation. Using viral genetics to selectively mimic and boost an endogenous learning-dependent circuit mechanism, DG cell recruitment of CA3 PV INs and feed-forward inhibition (FFI) in CA3, in combination with longitudinal in vivo calcium imaging, we demonstrate that FFI facilitates formation and maintenance of context-associated neuronal ensembles in CA1. Increasing FFI in DG - CA3 promoted context specificity of neuronal ensembles in ACC over time and enhanced long-term contextual fear memory. In vivo LFP recordings in mice with increased FFI in DG - CA3 identified enhanced CA1 sharp-wave ripple - ACC spindle coupling as a potential network mechanism facilitating memory consolidation. Our findings illuminate how FFI in DG - CA3 dictates evolution of ensemble properties in CA1 and ACC during memory consolidation and suggest a teacher-like function for hippocampal CA1 in stabilization and re-organization of cortical representations.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. GitHub link is provided. https://github.com/HannahTwarkowski/DG_CA3_FFI_consolidation

The following data sets were generated

1. Twarkowski H
(2021) DG_CA3_FFI_consolidation
GitHub.

https://github.com/HannahTwarkowski/DG_CA3_FFI_consolidation

Article and author information

Author details

Hannah Twarkowksi

Center for Regenerative Medicine, Massachusetts General Hospital, Boston, United States

Competing interests
No competing interests declared.
Victor Steininger

Center for Regenerative Medicine, Massachusetts General Hospital, Boston, United States

Competing interests
No competing interests declared.
Min Jae Kim

Center for Regenerative Medicine, Massachusetts General Hospital, Boston, United States

Competing interests
No competing interests declared.
Amar Sahay

Center for Regenerative Medicine, Massachusetts General Hospital, Boston, United States

For correspondence
asahay@mgh.harvard.edu

Competing interests
Amar Sahay, is a named inventor on a patent for targeting Ablim3 to improve memory (US Patent 10,287,580).

"This ORCID iD identifies the author of this article:" 0000-0003-0677-1693

Funding

DFG (German Research Foundation (DFG,TW 84/1-1) Postdoctoral fellowship)

Hannah Twarkowksi

NIH (NIH-NIA 1R01AG048908-01A1)

Amar Sahay

Simons Foundation (SCPAB)

Amar Sahay

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animals were handled, and experiments were conducted in strict accordance with proceduresapproved by the Institutional Animal Care and Use Committee at the Massachusetts General Hospital in accordance with NIH guidelines (IACUC 2011N000084).

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.