Neuronal sequences during theta rely on behavior-dependent spatial maps
Abstract
Navigation through space involves learning and representing relationships between past, current and future locations. In mammals, this might rely on the hippocampal theta phase code, where in each cycle of the theta oscillation, spatial representations provided by neuronal sequences start behind the animal's true location and then sweep forward. However, the exact relationship between theta phase, represented position and true location remains unclear and even paradoxical. Here, we formalize previous notions of 'spatial' or 'temporal' theta sweeps that have appeared in the literature. We analyze single-cell and population variables in unit recordings from rat CA1 place cells and compare them to model simulations based on each of these schemes. We show that neither spatial nor temporal sweeps quantitatively accounts for how all relevant variables change with running speed. To reconcile these schemes with our observations, we introduce 'behavior-dependent' sweeps, in which theta sweep length and place field properties, such as size and phase precession, vary across the environment depending on the running speed characteristic of each location. These behavior-dependent spatial maps provide a structured heterogeneity that is essential for understanding the hippocampal code.
Data availability
No new data was generated for this study. All analysis code has been made available at https://github.com/sencheng/models-and-analysis-of-theta-phase-coding
Article and author information
Author details
Funding
German Research Foundation (419037518 - FOR 2812,P2)
- Sen Cheng
German Federal Ministry of Education and Research (01GQ1506)
- Sen Cheng
National Institute of Mental Health (NIMH R01MH109170)
- Kamran Diba
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Laura L Colgin, University of Texas at Austin, United States
Publication history
- Preprint posted: April 14, 2021 (view preprint)
- Received: May 12, 2021
- Accepted: October 15, 2021
- Accepted Manuscript published: October 18, 2021 (version 1)
- Version of Record published: November 3, 2021 (version 2)
Copyright
© 2021, Parra-Barrero 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
-
- 1,277
- Page views
-
- 220
- Downloads
-
- 5
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.
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
-
- Genetics and Genomics
- Neuroscience
For at least two centuries, scientists have been enthralled by the “zombie” behaviors induced by mind-controlling parasites. Despite this interest, the mechanistic bases of these uncanny processes have remained mostly a mystery. Here, we leverage the Entomophthora muscae-Drosophila melanogaster “zombie fly” system to reveal the mechanistic underpinnings of summit disease, a manipulated behavior evoked by many fungal parasites. Using a high-throughput approach to measure summiting, we discovered that summiting behavior is characterized by a burst of locomotion and requires the host circadian and neurosecretory systems, specifically DN1p circadian neurons, pars intercerebralis to corpora allata projecting (PI-CA) neurons and corpora allata (CA), the latter being solely responsible for juvenile hormone (JH) synthesis and release. Using a machine learning classifier to identify summiting animals in real time, we observed that PI-CA neurons and CA appeared intact in summiting animals, despite invasion of adjacent regions of the “zombie fly” brain by E. muscae cells and extensive host tissue damage in the body cavity. The blood-brain barrier of flies late in their infection was significantly permeabilized, suggesting that factors in the hemolymph may have greater access to the central nervous system during summiting. Metabolomic analysis of hemolymph from summiting flies revealed differential abundance of several compounds compared to non-summiting flies. Transfusing the hemolymph of summiting flies into non-summiting recipients induced a burst of locomotion, demonstrating that factor(s) in the hemolymph likely cause summiting behavior. Altogether, our work reveals a neuro-mechanistic model for summiting wherein fungal cells perturb the fly’s hemolymph, activating a neurohormonal pathway linking clock neurons to juvenile hormone production in the CA, ultimately inducing locomotor activity in their host.
-
- Neuroscience
Deep brain stimulation targeting the posterior hypothalamus (pHyp-DBS) is being investigated as a treatment for refractory aggressive behavior, but its mechanisms of action remain elusive. We conducted an integrated imaging analysis of a large multi-centre dataset, incorporating volume of activated tissue modeling, probabilistic mapping, normative connectomics, and atlas-derived transcriptomics. Ninety-one percent of the patients responded positively to treatment, with a more striking improvement recorded in the pediatric population. Probabilistic mapping revealed an optimized surgical target within the posterior-inferior-lateral region of the posterior hypothalamic area. Normative connectomic analyses identified fiber tracts and functionally connected with brain areas associated with sensorimotor function, emotional regulation, and monoamine production. Functional connectivity between the target, periaqueductal gray and key limbic areas – together with patient age – were highly predictive of treatment outcome. Transcriptomic analysis showed that genes involved in mechanisms of aggressive behavior, neuronal communication, plasticity and neuroinflammation might underlie this functional network.