Multiple neurons encode CrebB dependent appetitive long-term memory in the mushroom body circuit
Abstract
Lasting changes in gene expression are critical for the formation of long-term memories (LTMs), depending on the conserved CrebB transcriptional activator. While requirement of distinct neurons in defined circuits for different learning and memory phases have been studied in detail, only little is known regarding the gene regulatory changes that occur within these neurons. We here use the fruit fly as powerful model system to study the neural circuits of CrebB-dependent appetitive olfactory LTM. We edited the CrebB locus to create a GFP-tagged CrebB conditional knockout allele, allowing us to generate mutant, post-mitotic neurons with high spatial and temporal precision. Investigating CrebB-dependence within the mushroom body (MB) circuit we show that MB α/β and α'/β' neurons as well as MBON α3, but not in dopaminergic neurons require CrebB for LTM. Thus, transcriptional memory traces occur in different neurons within the same neural circuit.
Data availability
All data is included in the manuscript.
Article and author information
Author details
Funding
Bundesbehörden der Schweizerischen Eidgenossenschaft (SynaptiX)
- Simon G Sprecher
Novartis Stiftung für Medizinisch-Biologische Forschung (18A017)
- Simon G Sprecher
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (CRSII5_180316)
- Simon G Sprecher
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Widmer 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
-
- 1,892
- views
-
- 284
- downloads
-
- 21
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
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)
Further reading
-
- Neuroscience
The remarkable ability of the motor system to adapt to novel environments has traditionally been investigated using kinematically non-redundant tasks, such as planar reaching movements. This limitation prevents the study of how the motor system achieves adaptation by altering the movement patterns of our redundant body. To address this issue, we developed a redundant motor task in which participants reached for targets with the tip of a virtual stick held with both hands. Despite the redundancy of the task, participants consistently employed a stereotypical strategy of flexibly changing the tilt angle of the stick depending on the direction of tip movement. Thus, this baseline relationship between tip-movement direction and stick-tilt angle constrained both the physical and visual movement patterns of the redundant system. Our task allowed us to systematically investigate how the motor system implicitly changed both the tip-movement direction and the stick-tilt angle in response to imposed visual perturbations. Both types of perturbations, whether directly affecting the task (tip-movement direction) or not (stick-tilt angle around the tip), drove adaptation, and the patterns of implicit adaptation were guided by the baseline relationship. Consequently, tip-movement adaptation was associated with changes in stick-tilt angle, and intriguingly, even seemingly ignorable stick-tilt perturbations significantly influenced tip-movement adaptation, leading to tip-movement direction errors. These findings provide a new understanding that the baseline relationship plays a crucial role not only in how the motor system controls movement of the redundant system, but also in how it implicitly adapts to modify movement patterns.
-
- Neuroscience
The relation between neural activity and behaviorally relevant variables is at the heart of neuroscience research. When strong, this relation is termed a neural representation. There is increasing evidence, however, for partial dissociations between activity in an area and relevant external variables. While many explanations have been proposed, a theoretical framework for the relationship between external and internal variables is lacking. Here, we utilize recurrent neural networks (RNNs) to explore the question of when and how neural dynamics and the network’s output are related from a geometrical point of view. We find that training RNNs can lead to two dynamical regimes: dynamics can either be aligned with the directions that generate output variables, or oblique to them. We show that the choice of readout weight magnitude before training can serve as a control knob between the regimes, similar to recent findings in feedforward networks. These regimes are functionally distinct. Oblique networks are more heterogeneous and suppress noise in their output directions. They are furthermore more robust to perturbations along the output directions. Crucially, the oblique regime is specific to recurrent (but not feedforward) networks, arising from dynamical stability considerations. Finally, we show that tendencies toward the aligned or the oblique regime can be dissociated in neural recordings. Altogether, our results open a new perspective for interpreting neural activity by relating network dynamics and their output.