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.
- 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
-
Differential electroresponsiveness of stellate and pyramidal-like cells of medial entorhinal cortex layer IIJournal of Neurophysiology 70:128–143.https://doi.org/10.1152/jn.1993.70.1.128
-
Cellular mechanisms of spatial navigation in the medial entorhinal cortexNature Neuroscience 16:325–331.https://doi.org/10.1038/nn.3340
Article and author information
Author details
Andrew S Alexander
Michael E Hasselmo
Publication history
- Version of Record published: September 14, 2018 (version 1)
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
-
- 1,088
- views
-
- 104
- downloads
-
- 0
- 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)
Navigation: Shedding light on stellate cells
eLife 7:e41041.
https://doi.org/10.7554/eLife.41041
Further reading
-
- Developmental Biology
- Neuroscience
Adolescence is characterized by changes in reward-related behaviors, social behaviors, and decision-making. These behavioral changes are necessary for the transition into adulthood, but they also increase vulnerability to the development of a range of psychiatric disorders. Major reorganization of the dopamine system during adolescence is thought to underlie, in part, the associated behavioral changes and increased vulnerability. Here, we utilized fast scan cyclic voltammetry and microdialysis to examine differences in dopamine release as well as mechanisms that underlie differential dopamine signaling in the nucleus accumbens (NAc) core of adolescent (P28-35) and adult (P70-90) male rats. We show baseline differences between adult and adolescent-stimulated dopamine release in male rats, as well as opposite effects of the α6 nicotinic acetylcholine receptor (nAChR) on modulating dopamine release. The α6-selective blocker, α-conotoxin, increased dopamine release in early adolescent rats, but decreased dopamine release in rats beginning in middle adolescence and extending through adulthood. Strikingly, blockade of GABAA and GABAB receptors revealed that this α6-mediated increase in adolescent dopamine release requires NAc GABA signaling to occur. We confirm the role of α6 nAChRs and GABA in mediating this effect in vivo using microdialysis. Results herein suggest a multisynaptic mechanism potentially unique to the period of development that includes early adolescence, involving acetylcholine acting at α6-containing nAChRs to drive inhibitory GABA tone on dopamine release.
-
- Neuroscience
Dopamine axons are the only axons known to grow during adolescence. Here, using rodent models, we examined how two proteins, Netrin-1 and its receptor, UNC5C, guide dopamine axons toward the prefrontal cortex and shape behaviour. We demonstrate in mice (Mus musculus) that dopamine axons reach the cortex through a transient gradient of Netrin-1-expressing cells – disrupting this gradient reroutes axons away from their target. Using a seasonal model (Siberian hamsters; Phodopus sungorus) we find that mesocortical dopamine development can be regulated by a natural environmental cue (daylength) in a sexually dimorphic manner – delayed in males, but advanced in females. The timings of dopamine axon growth and UNC5C expression are always phase-locked. Adolescence is an ill-defined, transitional period; we pinpoint neurodevelopmental markers underlying this period.
