Postsynaptic burst reactivation of hippocampal neurons enables associative plasticity of temporally discontiguous inputs
- University of Cambridge, United Kingdom
- Imperial College London, United Kingdom
- Michigan State University, United States
Abstract
A fundamental unresolved problem in neuroscience is how the brain associates in memory events that are separated in time. Here we propose that reactivation-induced synaptic plasticity can solve this problem. Previously, we reported that the reinforcement signal dopamine converts hippocampal spike timing-dependent depression into potentiation during continued synaptic activity (Brzosko et al., 2015). Here, we report that postsynaptic bursts in the presence of dopamine produce input-specific LTP in mouse hippocampal synapses 10 minutes after they were primed with coincident pre- and postsynaptic activity (post-before-pre pairing; Δt = -20 ms). This priming activity induces synaptic depression and sets an NMDA receptor-dependent silent eligibility trace which, through the cAMP-PKA cascade, is rapidly converted into protein synthesis-dependent synaptic potentiation, mediated by a signaling pathway distinct from that of conventional LTP. This synaptic learning rule was incorporated into a computational model, and we found that it adds specificity to reinforcement learning by controlling memory allocation and enabling both ‘instructive’ and 'supervised' reinforcement learning. We predicted that this mechanism would make reactivated neurons activate more strongly and carry more spatial information than non-reactivated cells, which was confirmed in freely moving mice performing a reward-based navigation task.
Data availability
Data availabilityExperimental data and code are available at:Code for computational model and code for in vivo analysis (including a link to in vivo data) are available at: https://github.com/przemyslawj/dCA1-reactivations. Data of plasticity experiments and of simulation data from computational model are available at: https://data.mendeley.com/datasets/dx7cdgpcz3/1.
Article and author information
Author details
Funding
Biotechnology and Biological Sciences Research Council (BB/N019008/1)
- Tanja Fuchsberger
- Zuzanna Brzosko
- Ole Paulsen
Biotechnology and Biological Sciences Research Council (BB/P019560/1)
- Tanja Fuchsberger
- Claudia Clopath
- Ole Paulsen
Biotechnology and Biological Sciences Research Council (Studentship)
- Przemyslaw Jarzebowski
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Marco Capogna, University of Aarhus, Denmark
Ethics
Animal experimentation: Experimental procedures and animal use were performed in accordance with UK Home Office regulations of the UK Animals (Scientific Procedures) Act 1986 and Amendment Regulations 2012, following ethical review by the University of Cambridge Animal Welfare and Ethical Review Body (AWERB). All animal procedures were authorized under Personal and Project licences held by the authors.
Version history
- Received: June 23, 2022
- Preprint posted: June 26, 2022 (view preprint)
- Accepted: October 9, 2022
- Accepted Manuscript published: October 13, 2022 (version 1)
- Version of Record published: October 27, 2022 (version 2)
Copyright
© 2022, Fuchsberger et al.
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.
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Postsynaptic burst reactivation of hippocampal neurons enables associative plasticity of temporally discontiguous inputs
eLife 11:e81071.
https://doi.org/10.7554/eLife.81071
Further reading
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Storing and accessing memories is required to successfully perform day-to-day tasks, for example for engaging in a meaningful conversation. Previous studies in both rodents and primates have correlated hippocampal cellular activity with behavioral expression of memory. A key role has been attributed to awake hippocampal replay – a sequential reactivation of neurons representing a trajectory through space. However, it is unclear if awake replay impacts immediate future behavior, gradually creates and stabilizes long-term memories over a long period of time (hours and longer), or enables the temporary memorization of relevant events at an intermediate time scale (seconds to minutes). In this study, we aimed to address the uncertainty around the timeframe of impact of awake replay by collecting causal evidence from behaving rats. We detected and disrupted sharp wave ripples (SWRs) - signatures of putative replay events - using electrical stimulation of the ventral hippocampal commissure in rats that were trained on three different spatial memory tasks. In each task, rats were required to memorize a new set of locations in each trial or each daily session. Interestingly, the rats performed equally well with or without SWR disruptions. These data suggest that awake SWRs - and potentially replay - does not affect the immediate behavior nor the temporary memorization of relevant events at a short timescale that are required to successfully perform the spatial tasks. Based on these results, we hypothesize that the impact of awake replay on memory and behavior is long-term and cumulative over time.
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