Uncovering temporal structure in hippocampal output patterns
Abstract
Place cell activity of hippocampal pyramidal cells has been described as the cognitive substrate of spatial memory. Replay is observed during hippocampal sharp-wave-ripple-associated population burst events (PBEs) and is critical for consolidation and recall-guided behaviors. PBE activity has historically been analyzed as a phenomenon subordinate to the place code. Here, we use hidden Markov models to study PBEs observed in rats during exploration of both linear mazes and open fields. We demonstrate that estimated models are consistent with a spatial map of the environment, and can even decode animals' positions during behavior. Moreover, we demonstrate the model can be used to identify hippocampal replay without recourse to the place code, using only PBE model congruence. These results suggest that downstream regions may rely on PBEs to provide a substrate for memory. Additionally, by forming models independent of animal behavior, we lay the groundwork for studies of non-spatial memory.
Data availability
We analyzed data from neural recording experiments. Data for Figures 1-5 has been previously reported in [1]. These data and also data for Figure 8 are available from Kamran Diba on request. Data for Figure 6 was previously reported in [2] and is available from Brad Pfeiffer and David Foster on request. Data for Figure 7 was previously reported in [3] is available from the CRCNS.org archive ('hc-6'). [1] Diba and Buzsaki, Nature Neuroscience, 2007 [2] Pfeiffer and Foster, Science, 2015 [3] Karlsson and Frank, Nature Neuroscience, 2009.All analysis code and sample recording epochs for Figures 1-7 are available on https://github.com/kemerelab/UncoveringTemporalStructureHippocampus. These make use of our broader open-source Python analysis software https://github.com/nelpy.
Article and author information
Author details
Funding
National Science Foundation (IOS-1550994)
- Etienne Ackermann
- Caleb Kemere
Human Frontier Science Program (RGY0088)
- Etienne Ackermann
- Caleb Kemere
Ken Kennedy Institute (ERIT)
- Caleb Kemere
National Institute of Mental Health (R01MH109170)
- Kourosh Maboudi
- Kamran Diba
National Institute of Mental Health (R01MH085823)
- Brad Pfeiffer
- David Foster
Alfred P. Sloan Foundation
- Brad Pfeiffer
- David Foster
Brain and Behavior Research Foundation (NARSAD Young Investigator Grant)
- Brad Pfeiffer
- David Foster
McKnight Endowment Fund for Neuroscience
- David Foster
National Science Foundation (CBET-1351692)
- Etienne Ackermann
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: As reported previously, all procedures were approved by the Johns Hopkins University, Rutgers University, and University of California, San Francisco Animal Care and Use Committees and followed US National Institutes of Health animal use guidelines (protocol 90-042).
Copyright
© 2018, Maboudi 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
-
- 5,894
- views
-
- 881
- downloads
-
- 56
- 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
Detecting causal relations structures our perception of events in the world. Here, we determined for visual interactions whether generalized (i.e. feature-invariant) or specialized (i.e. feature-selective) visual routines underlie the perception of causality. To this end, we applied a visual adaptation protocol to assess the adaptability of specific features in classical launching events of simple geometric shapes. We asked observers to report whether they observed a launch or a pass in ambiguous test events (i.e. the overlap between two discs varied from trial to trial). After prolonged exposure to causal launch events (the adaptor) defined by a particular set of features (i.e. a particular motion direction, motion speed, or feature conjunction), observers were less likely to see causal launches in subsequent ambiguous test events than before adaptation. Crucially, adaptation was contingent on the causal impression in launches as demonstrated by a lack of adaptation in non-causal control events. We assessed whether this negative aftereffect transfers to test events with a new set of feature values that were not presented during adaptation. Processing in specialized (as opposed to generalized) visual routines predicts that the transfer of visual adaptation depends on the feature similarity of the adaptor and the test event. We show that the negative aftereffects do not transfer to unadapted launch directions but do transfer to launch events of different speeds. Finally, we used colored discs to assign distinct feature-based identities to the launching and the launched stimulus. We found that the adaptation transferred across colors if the test event had the same motion direction as the adaptor. In summary, visual adaptation allowed us to carve out a visual feature space underlying the perception of causality and revealed specialized visual routines that are tuned to a launch’s motion direction.
-
- Neuroscience
The classical diagnosis of Parkinsonism is based on motor symptoms that are the consequence of nigrostriatal pathway dysfunction and reduced dopaminergic output. However, a decade prior to the emergence of motor issues, patients frequently experience non-motor symptoms, such as a reduced sense of smell (hyposmia). The cellular and molecular bases for these early defects remain enigmatic. To explore this, we developed a new collection of five fruit fly models of familial Parkinsonism and conducted single-cell RNA sequencing on young brains of these models. Interestingly, cholinergic projection neurons are the most vulnerable cells, and genes associated with presynaptic function are the most deregulated. Additional single nucleus sequencing of three specific brain regions of Parkinson’s disease patients confirms these findings. Indeed, the disturbances lead to early synaptic dysfunction, notably affecting cholinergic olfactory projection neurons crucial for olfactory function in flies. Correcting these defects specifically in olfactory cholinergic interneurons in flies or inducing cholinergic signaling in Parkinson mutant human induced dopaminergic neurons in vitro using nicotine, both rescue age-dependent dopaminergic neuron decline. Hence, our research uncovers that one of the earliest indicators of disease in five different models of familial Parkinsonism is synaptic dysfunction in higher-order cholinergic projection neurons and this contributes to the development of hyposmia. Furthermore, the shared pathways of synaptic failure in these cholinergic neurons ultimately contribute to dopaminergic dysfunction later in life.