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Elife. 2020 Feb 13;9. pii: e52258. doi: 10.7554/eLife.52258.

Inter- and intra-animal variation in the integrative properties of stellate cells in the medial entorhinal cortex.

Author information

1
Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.
2
The Alan Turing Institute, London, United States.
3
School of Mathematics, Maxwell Institute and Centre for Statistics, University of Edinburgh, Edinburgh, United Kingdom.

Abstract

Distinctions between cell types underpin organizational principles for nervous system function. Functional variation also exists between neurons of the same type. This is exemplified by correspondence between grid cell spatial scales and the synaptic integrative properties of stellate cells (SCs) in the medial entorhinal cortex. However, we know little about how functional variability is structured either within or between individuals. Using ex-vivo patch-clamp recordings from up to 55 SCs per mouse, we found that integrative properties vary between mice and, in contrast to the modularity of grid cell spatial scales, have a continuous dorsoventral organization. Our results constrain mechanisms for modular grid firing and provide evidence for inter-animal phenotypic variability among neurons of the same type. We suggest that neuron type properties are tuned to circuit-level set points that vary within and between animals.

plain-language-summary:

The brain consists of many types of cells that are specialised to perform different tasks. This is similar to how different groups of people will have different responsibilities in a large company. But within each group with the same role, individual employees will also do their jobs in different ways. Does the same apply to the brain? In other words, do individual neurons of the same type – with the same role – process information differently? To find out, Pastoll et al. studied stellate cells in the mouse brain: these neurons take their name from their distinctive star-shaped arrays of projections, and they work together in groups known as modules to help animals navigate their environment. To determine whether stellate cells differ between mice, and how they might differ within a single animal, Pastoll et al. measured the activity of more than 800 stellate cells in more than two dozen individuals. The results revealed that stellate cells process the same information differently between mice, which may contribute to variations in behaviour across the species. But even within an individual, stellate cells also showed differences in information processing. In fact, the properties of the stellate cells within each mouse varied along a continuum. This discovery rules out several previous theories on how stellate cells form the modules that support navigation. The work by Pastoll et al. helps to understand how the brain supports thinking and memory. In the long term, these findings could also have implications for treating brain disorders, as they suggest that variations between people in the properties of their neurons could lead to variations in drug response. Researchers may need to take inter-individual differences into account when planning experiments, and ultimately when designing drugs.

KEYWORDS:

entorhinal cortex; mouse; multi-vesicular release; neuroscience; presynaptic function; synaptic integration; synaptic vesicle

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