Navigation: Shedding light on stellate cells

The relationship between grid cells and two types of neurons found in the medial entorhinal cortex has been clarified.
  1. Andrew S Alexander  Is a corresponding author
  2. Michael E Hasselmo  Is a corresponding author
  1. Boston University, United States

Most people can remember the floorplan of their current home and the layout of their local supermarket. They might also be able to create a virtual map of their current location, their home and the supermarket, which allows them to mentally navigate from one place to the next. Our sense of location depends on a network of regions in the brain, including the hippocampus and its neighbor, the medial entorhinal cortex (MEC).

The different types of neurons within these structures work together to form a sort of inbuilt GPS that tracks our position relative to other objects or places in the environment. In the hippocampus, place cells are activated when an animal occupies a single position in the environment (O'Keefe and Dostrovsky, 1971). In the MEC, head direction cells and border cells become active when an animal faces a particular direction or is near a border (Sargolini et al., 2006; Solstad et al., 2008). The MEC also contains grid cells that – much like the black squares on a chess board – represent multiple equally-spaced locations in an environment via their firing patterns (Hafting et al., 2005).

Previous research has shown that the inputs of the MEC into the hippocampus – in particular from the grid cells – are potentially crucial for the spatial and memory functions (Schlesiger et al., 2015). Grid cells reside predominantly in an area of the MEC known as layer II, where two morphologically distinct sub-populations of neurons, the stellate and pyramidal cells, exist.

Both stellate and pyramidal cells have different physiological properties and connect to the hippocampus through different pathways (Alonso and Klink, 1993). Stellate cells form a prominent connection directly into multiple sub-regions of the hippocampus, while the density of the connections between the pyramidal neurons and the hippocampus is significantly less. However, the exact role of stellate and pyramidal cells has so far remained unclear.

Several studies have reported that both stellate and pyramidal cells could be grid cells, while others found that the proportion of grid cells within the stellate sub-population was virtually nonexistent (Domnisoru et al., 2013; Schmidt-Hieber and Häusser, 2013; Tang et al., 2014). Thus, it has remained unclear whether MEC neurons that exhibit grid firing or other spatial responses belong to the sub-class of MEC layer II cells that do indeed project into the hippocampus.

Now, in eLife, May-Britt Moser and colleagues at the Norwegian University of Science and Technology – including David Rowland as first author – report new insights into these cells (Rowland et al., 2018). Using sophisticated genetic tools paired with electrical recordings from single neurons in free-moving mice, they could assess the relationship between stellate and pyramidal cell sub-populations, and other known spatial coding neurons within the MEC layer II.

Rowland et al. used a technique called optogenetics, in which genetically modified neurons that produce light-sensitive proteins can either be activated or silenced with light. The mouse model used in the experiments expressed a light-sensitive protein called ArchT in the stellate cells of layer II, which meant that these neurons could be shut off by exposing them to light of a specific wavelength.

Rowland et al. measured the activity of layer II neurons while the mice freely explored an open space. Then, the same neurons were recorded while simultaneously exposed to light (a process referred to as ‘phototagging’). All cells that were silenced within moments of the light onset were ‘tagged’ as layer II stellate cells. This allowed a comparison of firing properties during the free-foraging session between the tagged stellate neurons and untagged populations composed primarily of pyramidal cells.

The results showed that the tagged stellate cell population had similar, if not stronger, spatial firing properties compared to the untagged cell population. Grid cells existed in similar numbers in both the tagged stellate and untagged populations. This suggests that the stellate cells projecting into the hippocampus include cells from a range of functional cell types and thus, may help the hippocampus to process information about location.

The work of Rowland et al. has resolved discrepancies between previous reports and brought to light important questions. For example, how do stellate grid cells, pyramidal grid cells and other types of spatial cells shape spatial processing and memory, and are there any differences between them? To what degree do these morphologically distinct, yet functionally overlapping, sub-populations depend on one another? These questions aside, the latest work demonstrates the power of phototagging as a means to better characterize circuit-specific projections within the brain regions that support navigation.

References

Article and author information

Author details

  1. Andrew S Alexander

    Andrew S Alexander is in the Department of Psychological and Brain Sciences, Boston University, Boston, United States

    For correspondence
    asalexan@bu.edu
    Competing interests
    No competing interests declared
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1735-3449
  2. Michael E Hasselmo

    Michael E Hasselmo is in the Department of Psychological and Brain Sciences, Boston University, Boston, United States

    For correspondence
    hasselmo@gmail.com
    Competing interests
    No competing interests declared
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9925-6377

Publication history

  1. Version of Record published:

Copyright

© 2018, Alexander et al.

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,105
    views
  • 104
    downloads
  • 1
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

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)

  1. Andrew S Alexander
  2. Michael E Hasselmo
(2018)
Navigation: Shedding light on stellate cells
eLife 7:e41041.
https://doi.org/10.7554/eLife.41041
  1. Further reading

Further reading

    1. Neuroscience
    Rossella Conti, Céline Auger
    Research Article

    Granule cells of the cerebellum make up to 175,000 excitatory synapses on a single Purkinje cell, encoding the wide variety of information from the mossy fibre inputs into the cerebellar cortex. The granule cell axon is made of an ascending portion and a long parallel fibre extending at right angles, an architecture suggesting that synapses formed by the two segments of the axon could encode different information. There are controversial indications that ascending axon (AA) and parallel fibre (PF) synapse properties and modalities of plasticity are different. We tested the hypothesis that AA and PF synapses encode different information, and that the association of these distinct inputs to Purkinje cells might be relevant to the circuit and trigger plasticity, similar to the coincident activation of PF and climbing fibre inputs. Here, by recording synaptic currents in Purkinje cells from either proximal or distal granule cells (mostly AA and PF synapses, respectively), we describe a new form of associative plasticity between these two distinct granule cell inputs. We show for the first time that synchronous AA and PF repetitive train stimulation, with inhibition intact, triggers long-term potentiation (LTP) at AA synapses specifically. Furthermore, the timing of the presentation of the two inputs controls the outcome of plasticity and induction requires NMDAR and mGluR1 activation. The long length of the PFs allows us to preferentially activate the two inputs independently, and despite a lack of morphological reconstruction of the connections, these observations reinforce the suggestion that AA and PF synapses have different coding capabilities and plasticity that is associative, enabling effective association of information transmitted via granule cells.

    1. Neuroscience
    Yiting Li, Wenqu Yin ... Baoming Li
    Research Article

    Time estimation is an essential prerequisite underlying various cognitive functions. Previous studies identified ‘sequential firing’ and ‘activity ramps’ as the primary neuron activity patterns in the medial frontal cortex (mPFC) that could convey information regarding time. However, the relationship between these patterns and the timing behavior has not been fully understood. In this study, we utilized in vivo calcium imaging of mPFC in rats performing a timing task. We observed cells that showed selective activation at trial start, end, or during the timing interval. By aligning long-term time-lapse datasets, we discovered that sequential patterns of time coding were stable over weeks, while cells coding for trial start or end showed constant dynamism. Furthermore, with a novel behavior design that allowed the animal to determine individual trial interval, we were able to demonstrate that real-time adjustment in the sequence procession speed closely tracked the trial-to-trial interval variations. And errors in the rats’ timing behavior can be primarily attributed to the premature ending of the time sequence. Together, our data suggest that sequential activity maybe a stable neural substrate that represents time under physiological conditions. Furthermore, our results imply the existence of a unique cell type in the mPFC that participates in the time-related sequences. Future characterization of this cell type could provide important insights in the neural mechanism of timing and related cognitive functions.