Effects of visual inputs on neural dynamics for coding of location and running speed in medial entorhinal cortex

Abstract

Neuronal representations of spatial location and movement speed in the medial entorhinal cortex during the 'active' theta state of the brain are important for memory-guided navigation and rely on visual inputs. However, little is known about how visual inputs change neural dynamics as a function of running speed and time. By manipulating visual inputs in mice, we demonstrate that changes in spatial stability of grid cell firing correlate with changes in a proposed speed signal by local field potential theta frequency. In contrast, visual inputs do not alter the running speed-dependent gain in neuronal firing rates. Moreover, we provide evidence that sensory inputs other than visual inputs can support grid cell firing, though less accurately, in complete darkness. Finally, changes in spatial accuracy of grid cell firing on a 10 s time scale suggest that grid cell firing is a function of velocity signals integrated over past time.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files. Matlab code for Figure 4 is provided on the laboratory's GitHub page (https://github.com/hasselmonians/light-modulation and https://github.com/hasselmonians/mle_rhythmicity). Source data files have been provided for Figures 2, 3, 4, 5, and 6.

Article and author information

Author details

  1. Holger Dannenberg

    Psychological & Brain Sciences, Boston University, Boston, United States
    For correspondence
    hdannenb@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0340-0128
  2. Hallie Lazaro

    Psychological & Brain Sciences, Boston University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Pranav Nambiar

    Psychological & Brain Sciences, Boston University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Alec Hoyland

    Psychological & Brain Sciences, Boston University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4732-5932
  5. Michael E. Hasselmo

    Psychological & Brain Sciences, Boston University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9925-6377

Funding

National Institutes of Health (R01MH60013)

  • Holger Dannenberg
  • Hallie Lazaro
  • Pranav Nambiar
  • Alec Hoyland
  • Michael E. Hasselmo

National Institutes of Health (R01MH120073)

  • Holger Dannenberg
  • Hallie Lazaro
  • Pranav Nambiar
  • Alec Hoyland
  • Michael E. Hasselmo

National Institutes of Health (R01MH052090)

  • Holger Dannenberg
  • Hallie Lazaro
  • Pranav Nambiar
  • Alec Hoyland
  • Michael E. Hasselmo

National Institutes of Health (K99NS116129)

  • Holger Dannenberg

Office of Naval Research (MURI N00014-16-1-2832)

  • Holger Dannenberg
  • Hallie Lazaro
  • Pranav Nambiar
  • Alec Hoyland
  • Michael E. Hasselmo

Office of Naval Research (MURI N00014-19-1-2571)

  • Holger Dannenberg
  • Hallie Lazaro
  • Pranav Nambiar
  • Alec Hoyland
  • Michael E. Hasselmo

Office of Naval Research (DURIP N00014-17-1-2304)

  • Holger Dannenberg
  • Hallie Lazaro
  • Pranav Nambiar
  • Alec Hoyland
  • Michael E. Hasselmo

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All handling of animals and experimental procedures were approved by the Institutional Animal Care and Use Committee (IACUC) for the Charles River Campus at Boston University under protocol #16-008 . All surgery was performed under isoflurane anesthesia and buprenorphine analgesia, and every effort was made to minimize suffering.

Copyright

© 2020, Dannenberg 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.

Download links

Share this article

https://doi.org/10.7554/eLife.62500

Further reading

    1. Neuroscience
    Gergely F Turi, Sasa Teng ... Yueqing Peng
    Research Article

    Synchronous neuronal activity is organized into neuronal oscillations with various frequency and time domains across different brain areas and brain states. For example, hippocampal theta, gamma, and sharp wave oscillations are critical for memory formation and communication between hippocampal subareas and the cortex. In this study, we investigated the neuronal activity of the dentate gyrus (DG) with optical imaging tools during sleep-wake cycles in mice. We found that the activity of major glutamatergic cell populations in the DG is organized into infraslow oscillations (0.01–0.03 Hz) during NREM sleep. Although the DG is considered a sparsely active network during wakefulness, we found that 50% of granule cells and about 25% of mossy cells exhibit increased activity during NREM sleep, compared to that during wakefulness. Further experiments revealed that the infraslow oscillation in the DG was correlated with rhythmic serotonin release during sleep, which oscillates at the same frequency but in an opposite phase. Genetic manipulation of 5-HT receptors revealed that this neuromodulatory regulation is mediated by Htr1a receptors and the knockdown of these receptors leads to memory impairment. Together, our results provide novel mechanistic insights into how the 5-HT system can influence hippocampal activity patterns during sleep.

    1. Neuroscience
    Ulrike Pech, Jasper Janssens ... Patrik Verstreken
    Research Article

    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.