Inter-and intra-animal variation in the integrative properties of stellate cells in the medial entorhinal cortex
- University of Edinburgh, United Kingdom
Abstract
Distinctions between cell types underpin organisational 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 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 find that integrative properties vary between mice and, in contrast to modularity of grid cell spatial scales, have a continuous dorsoventral organisation. 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.
Data availability
Processed data used for analyses and all associated code is available from the GitHub page for the project (https://github.com/MattNolanLab/Inter_Intra_Variation).Raw data has been made available from our institutional repository and can be found under the DOI 10.7488/ds/2765. Scripts that generate the processed data from the raw data will be made available from our GitHub site. We expect to complete documention of these scripts in the next few weeks. We will make the data and scripts freely available when this is complete.
Article and author information
Author details
Funding
Wellcome (200855/Z/16/Z)
- Matthew F Nolan
Biotechnology and Biological Sciences Research Council (BB/L010496/1)
- Matthew F Nolan
Biotechnology and Biological Sciences Research Council (BB/1022147/1)
- Matthew F Nolan
Biotechnology and Biological Sciences Research Council (BB/H020284/1)
- Matthew F Nolan
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experimental procedures were performed under a United Kingdom Home Office license (PC198F2A0) and with approval of the University of Edinburgh's animal welfare committee.
Copyright
© 2020, Pastoll 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.
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Inter-and intra-animal variation in the integrative properties of stellate cells in the medial entorhinal cortex
eLife 9:e52258.
https://doi.org/10.7554/eLife.52258
Further reading
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Dense core vesicles (DCVs) transport and release various neuropeptides and neurotrophins that control diverse brain functions, but the DCV secretory pathway remains poorly understood. Here, we tested a prediction emerging from invertebrate studies about the crucial role of the intracellular trafficking GTPase Rab10, by assessing DCV exocytosis at single-cell resolution upon acute Rab10 depletion in mature mouse hippocampal neurons, to circumvent potential confounding effects of Rab10’s established role in neurite outgrowth. We observed a significant inhibition of DCV exocytosis in Rab10-depleted neurons, whereas synaptic vesicle exocytosis was unaffected. However, rather than a direct involvement in DCV trafficking, this effect was attributed to two ER-dependent processes, ER-regulated intracellular Ca2+ dynamics, and protein synthesis. Gene Ontology analysis of differentially expressed proteins upon Rab10 depletion identified substantial alterations in synaptic and ER/ribosomal proteins, including the Ca2+ pump SERCA2. In addition, ER morphology and dynamics were altered, ER Ca2+ levels were depleted, and Ca2+ homeostasis was impaired in Rab10-depleted neurons. However, Ca2+ entry using a Ca2+ ionophore still triggered less DCV exocytosis. Instead, leucine supplementation, which enhances protein synthesis, largely rescued DCV exocytosis deficiency. We conclude that Rab10 is required for neuropeptide release by maintaining Ca2+ dynamics and regulating protein synthesis. Furthermore, DCV exocytosis appeared more dependent on (acute) protein synthesis than synaptic vesicle exocytosis.
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By influencing calcium homeostasis, local protein synthesis and the endoplasmic reticulum, a small protein called Rab10 emerges as a crucial cytoplasmic regulator of neuropeptide secretion.
