Phase-tuned neuronal firing encodes human contextual representations for navigational goals
Abstract
We previously demonstrated that the phase of oscillations modulates neural activity representing categorical information using human intracranial recordings and high-frequency activity from local field potentials (Watrous et al., 2015b). We extend these findings here using human single-neuron recordings during a navigation task. We identify neurons in the medial temporal lobe with firing-rate modulations for specific navigational goals, as well as for navigational planning and goal arrival. Going beyond this work, using a novel oscillation detection algorithm, we identify phase-locked neural firing that encodes information about a person's prospective navigational goal in the absence of firing rate changes. These results provide evidence for navigational planning and contextual accounts of human MTL function at the single-neuron level. More generally, our findings identify phase-coded neuronal firing as a component of the human neural code.
Data availability
The human single neuron recordings raw data can be obtained upon request from Joshua Jacobs (joshua.jacobs@columbia.edu). At this point, the raw data has not been made publicly available to ensure controlled access to the dataset and that the patients' anonymity is not compromised.
-
Simultaneous electrophysiological recordings of ensembles of isolated neurons in rat medial prefrontal cortex and intermediate CA1 area of the hippocampus during a working memory taskPublicly available at CRCNS.org. - Collaborative Research in Computational Neuroscience.
Article and author information
Author details
Funding
National Institute of Neurological Disorders and Stroke (NS033221)
- Itzhak Fried
National Institute of Neurological Disorders and Stroke (NS084017)
- Itzhak Fried
National Institute of Mental Health (MH104606)
- Joshua Jacobs
National Science Foundation (DGE 16-44869)
- Salman E Qasim
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: The Medical Institutional Review Board at the University of California-Los Angeles approved this study (IRB#10-000973) involving recordings from patients with drug-resistant epilepsy who provided informed consent to participate in research.
Copyright
© 2018, Watrous 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
-
- 3,224
- views
-
- 467
- downloads
-
- 95
- 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
- Physics of Living Systems
Neurons generate and propagate electrical pulses called action potentials which annihilate on arrival at the axon terminal. We measure the extracellular electric field generated by propagating and annihilating action potentials and find that on annihilation, action potentials expel a local discharge. The discharge at the axon terminal generates an inhomogeneous electric field that immediately influences target neurons and thus provokes ephaptic coupling. Our measurements are quantitatively verified by a powerful analytical model which reveals excitation and inhibition in target neurons, depending on position and morphology of the source-target arrangement. Our model is in full agreement with experimental findings on ephaptic coupling at the well-studied Basket cell-Purkinje cell synapse. It is able to predict ephaptic coupling for any other synaptic geometry as illustrated by a few examples.
-
- 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.