Axon TRAP reveals learning-associated alterations in cortical axonal mRNAs in the lateral amgydala
- University of Connecticut, United States
- Karolinska Institutet, Sweden
- New York University, United States
- New York University School of Medicine, United States
Abstract
Local translation can support memory consolidation by supplying new proteins to synapses undergoing plasticity. Translation in adult forebrain dendrites is an established mechanism of synaptic plasticity and is regulated by learning, yet there is no evidence for learning-regulated protein synthesis in adult forebrain axons, which have traditionally been believed to be incapable of translation. Here we show that axons in the adult rat amygdala contain translation machinery, and use translating ribosome affinity purification (TRAP) with RNASeq to identify mRNAs in cortical axons projecting to the amygdala, over 1200 of which were regulated during consolidation of associative memory. Mitochondrial and translation-related genes were upregulated, whereas synaptic, cytoskeletal, and myelin-related genes were downregulated; the opposite effects were observed in the cortex. Our results demonstrate that axonal translation occurs in the adult forebrain and is altered after learning, supporting the likelihood that local translation is more a rule than an exception in neuronal processes.
Data availability
Sequencing data have been deposited in GEO under accession code GSE124592. All analyses are included in supporting files.
-
The translatome of adult cortical neurons is regulated by learning in vivoNCBI Gene Expression Omnibus, GSE124592.
Article and author information
Author details
Funding
National Institute of Neurological Disorders and Stroke (NS034007)
- Eric Klann
Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD082013)
- Eric Klann
National Institute of Mental Health (MH083583)
- Linnaea E Ostroff
National Institute of Neurological Disorders and Stroke (NS047384)
- Eric Klann
National Institute of Mental Health (MH094965)
- Linnaea E Ostroff
National Institute of Mental Health (MH119517)
- Linnaea E Ostroff
National Institute of Neurological Disorders and Stroke (NS087112)
- Emanuela Santini
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Robert H Singer, Albert Einstein College of Medicine, United States
Ethics
Animal experimentation: All animal procedures were performed in accordance with the guidelines in the National Institutes of Health Guide for the Care and Use of Laboratory Animals, and were approved by the Animal Care and Use Committees of New York University (protocol 01-1097) and the University of Connecticut (protocol A17-036).
Version history
- Received: September 4, 2019
- Accepted: December 10, 2019
- Accepted Manuscript published: December 11, 2019 (version 1)
- Version of Record published: December 20, 2019 (version 2)
- Version of Record updated: July 13, 2020 (version 3)
Copyright
© 2019, Ostroff 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.
Metrics
-
- 4,390
- views
-
- 624
- downloads
-
- 52
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Axon TRAP reveals learning-associated alterations in cortical axonal mRNAs in the lateral amgydala
eLife 8:e51607.
https://doi.org/10.7554/eLife.51607
Further reading
-
- Neuroscience
Synaptic inputs to cortical neurons are highly structured in adult sensory systems, such that neighboring synapses along dendrites are activated by similar stimuli. This organization of synaptic inputs, called synaptic clustering, is required for high-fidelity signal processing, and clustered synapses can already be observed before eye opening. However, how clustered inputs emerge during development is unknown. Here, we employed concurrent in vivo whole-cell patch-clamp and dendritic calcium imaging to map spontaneous synaptic inputs to dendrites of layer 2/3 neurons in the mouse primary visual cortex during the second postnatal week until eye opening. We found that the number of functional synapses and the frequency of transmission events increase several fold during this developmental period. At the beginning of the second postnatal week, synapses assemble specifically in confined dendritic segments, whereas other segments are devoid of synapses. By the end of the second postnatal week, just before eye opening, dendrites are almost entirely covered by domains of co-active synapses. Finally, co-activity with their neighbor synapses correlates with synaptic stabilization and potentiation. Thus, clustered synapses form in distinct functional domains presumably to equip dendrites with computational modules for high-capacity sensory processing when the eyes open.
-
- Neuroscience
Accurate tracking of the same neurons across multiple days is crucial for studying changes in neuronal activity during learning and adaptation. Advances in high-density extracellular electrophysiology recording probes, such as Neuropixels, provide a promising avenue to accomplish this goal. Identifying the same neurons in multiple recordings is, however, complicated by non-rigid movement of the tissue relative to the recording sites (drift) and loss of signal from some neurons. Here, we propose a neuron tracking method that can identify the same cells independent of firing statistics, that are used by most existing methods. Our method is based on between-day non-rigid alignment of spike-sorted clusters. We verified the same cell identity in mice using measured visual receptive fields. This method succeeds on datasets separated from 1 to 47 days, with an 84% average recovery rate.
