Synchronized excitability in a network enables generation of internal neuronal sequences
- Janelia Farm Research Campus, Howard Hughes Medical Institute, United States
Abstract
Hippocampal place field sequences are supported by sensory cues and network internal mechanisms. In contrast, sharp-wave (SPW) sequences, theta sequences and episode-field sequences are internally generated. The relationship of these sequences to memory is unclear. SPW sequences have been shown to support learning and have been assumed to also support episodic memory. Conversely, we demonstrate these SPW sequences were present even after episodic memory in trained rats was impaired and after other internal sequences - episode-field and theta sequences - were eliminated. SPW sequences did not support memory despite continuing to 'replay' all task-related sequences - place-field and episode-field sequences. Sequence replay occurred selectively during a synchronous increase of population excitability -- SPWs. Similarly, theta sequences depended on the presence of repeated synchronized waves of excitability - theta oscillations. Thus, we suggest that either intermittent or rhythmic synchronized changes of excitability trigger sequential firing of neurons, which in turn supports learning and/or memory.
Article and author information
Author details
Funding
Howard Hughes Medical Institute
- Wang Yingxue
- Zachary Roth
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 of the animals were handled according to approved institutional animal care and use committee (IACUC) of Janelia Research Campus, HHMI: protocols 10-59 and #13-96.
Copyright
© 2016, Yingxue 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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Synchronized excitability in a network enables generation of internal neuronal sequences
eLife 5:e20697.
https://doi.org/10.7554/eLife.20697
Further reading
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- Neuroscience
Pain is heavily modulated by expectations. Whereas the integration of expectations with sensory information has been examined in some detail, little is known about how positive and negative expectations are generated and their neural dynamics from generation over anticipation to the integration with sensory information. The present preregistered study employed a novel paradigm to induce positive and negative expectations on a trial-by-trial basis and examined the neural mechanisms using combined EEG-fMRI measurements (n=50). We observed substantially different neural representations between the anticipatory and the actual pain period. In the anticipation phase i.e., before the nociceptive input, the insular cortex, dorsolateral prefrontal cortex (DLPFC), and anterior cingulate cortex (ACC) showed increased activity for directed expectations regardless of their valence. Interestingly, a differentiation between positive and negative expectations within the majority of areas only occurred after the arrival of nociceptive information. FMRI-informed EEG analyses could reliably track the temporal sequence of processing showing an early effect in the DLPFC, followed by the anterior insula and late effects in the ACC. The observed effects indicate the involvement of different expectation-related subprocesses, including the transformation of visual information into a value signal that is maintained and differentiated according to its valence only during stimulus processing.
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- Medicine
- Neuroscience
Background:
Alcohol use disorder (AUD) is a global health problem with limited therapeutic options. The biochemical mechanisms that lead to this disorder are not yet fully understood, and in this respect, metabolomics represents a promising approach to decipher metabolic events related to AUD. The plasma metabolome contains a plethora of bioactive molecules that reflects the functional changes in host metabolism but also the impact of the gut microbiome and nutritional habits.
Methods:
In this study, we investigated the impact of severe AUD (sAUD), and of a 3-week period of alcohol abstinence, on the blood metabolome (non-targeted LC-MS metabolomics analysis) in 96 sAUD patients hospitalized for alcohol withdrawal.
Results:
We found that the plasma levels of different lipids ((lyso)phosphatidylcholines, long-chain fatty acids), short-chain fatty acids (i.e. 3-hydroxyvaleric acid) and bile acids were altered in sAUD patients. In addition, several microbial metabolites, including indole-3-propionic acid, p-cresol sulfate, hippuric acid, pyrocatechol sulfate, and metabolites belonging to xanthine class (paraxanthine, theobromine and theophylline) were sensitive to alcohol exposure and alcohol withdrawal. 3-Hydroxyvaleric acid, caffeine metabolites (theobromine, paraxanthine, and theophylline) and microbial metabolites (hippuric acid and pyrocatechol sulfate) were correlated with anxiety, depression and alcohol craving. Metabolomics analysis in postmortem samples of frontal cortex and cerebrospinal fluid of those consuming a high level of alcohol revealed that those metabolites can be found also in brain tissue.
Conclusions:
Our data allow the identification of neuroactive metabolites, from interactions between food components and microbiota, which may represent new targets arising in the management of neuropsychiatric diseases such as sAUD.
Funding:
Gut2Behave project was initiated from ERA-NET NEURON network (Joint Transnational Call 2019) and was financed by Academy of Finland, French National Research Agency (ANR-19-NEUR-0003-03) and the Fonds de la Recherche Scientifique (FRS-FNRS; PINT-MULTI R.8013.19, Belgium). Metabolomics analysis of the TSDS samples was supported by grant from the Finnish Foundation for Alcohol Studies.
