Fan cells in lateral entorhinal cortex directly influence medial entorhinal cortex through synaptic connections in layer 1
- University of Edinburgh, United Kingdom
Abstract
Standard models for spatial and episodic memory suggest that the lateral entorhinal cortex (LEC) and medial entorhinal cortex (MEC) send parallel independent inputs to the hippocampus, each carrying different types of information. Here, we evaluate the possibility that information is integrated between divisions of the entorhinal cortex prior to reaching the hippocampus. We demonstrate that, in mice, fan cells in layer 2 (L2) of LEC that receive neocortical inputs, and that project to the hippocampal dentate gyrus, also send axon collaterals to layer 1 (L1) of the MEC. Activation of inputs from fan cells evokes monosynaptic glutamatergic excitation of stellate and pyramidal cells in L2 of the MEC, typically followed by inhibition that contains fast and slow components mediated by GABAA and GABAB receptors, respectively. Inputs from fan cells also directly activate interneurons in L1 and L2 of MEC, with synaptic connections from L1 interneurons accounting for slow feedforward inhibition of L2 principal cell populations. The relative strength of excitation and inhibition following fan cell activation differs substantially between neurons and is largely independent of anatomical location. Our results demonstrate that the LEC, in addition to directly influencing the hippocampus, can activate or inhibit major hippocampal inputs arising from the MEC. Thus, local circuits in the superficial MEC may combine spatial information with sensory and higher order signals from the LEC, providing a substrate for integration of 'what' and 'where' components of episodic memories.
Data availability
Data is available at: https://datashare.ed.ac.uk/handle/10283/4774Source data and code is available at https://github.com/MattNolanLab/lec_to_mec.
-
lec_to_mecGithub, https://github.com/MattNolanLab/lec_to_mec.
Article and author information
Author details
Funding
Wellcome Trust (200855/Z/16/Z)
- Matthew F Nolan
Biotechnology and Biological Sciences Research Council (BB/V010107/1)
- Brianna Vandrey
- 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: ll experiments and surgeries were pre-approved by a veterinarian at the Universityof Edinburgh, and conducted under a project licence administered by the UK Home Officeand in accordance with national (Animal [Scientific Procedures] Act, 1986) and international(European Communities Council Directive 2010 (2010/63/EU) legislation governing themaintenance of laboratory animals and their use in scientific research. In reporting results ofanimal research we have aimed to follow the ARRIVE guidelines.
Copyright
© 2022, Vandrey 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.
Metrics
-
- 1,665
- views
-
- 216
- downloads
-
- 11
- 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)
Fan cells in lateral entorhinal cortex directly influence medial entorhinal cortex through synaptic connections in layer 1
eLife 11:e83008.
https://doi.org/10.7554/eLife.83008
Further reading
-
- Neuroscience
Control of voluntary limb movement is predominantly attributed to the contralateral motor cortex. However, increasing evidence suggests the involvement of ipsilateral cortical networks in this process, especially in motor tasks requiring bilateral coordination, such as locomotion. In this study, we combined a unilateral thoracic spinal cord injury (SCI) with a cortical neuroprosthetic approach to investigate the functional role of the ipsilateral motor cortex in rat movement through spared contralesional pathways. Our findings reveal that in all SCI rats, stimulation of the ipsilesional motor cortex promoted a bilateral synergy. This synergy involved the elevation of the contralateral foot along with ipsilateral hindlimb extension. Additionally, in two out of seven animals, stimulation of a sub-region of the hindlimb motor cortex modulated ipsilateral hindlimb flexion. Importantly, ipsilateral cortical stimulation delivered after SCI immediately alleviated multiple locomotor and postural deficits, and this effect persisted after ablation of the homologous motor cortex. These results provide strong evidence of a causal link between cortical activation and precise ipsilateral control of hindlimb movement. This study has significant implications for the development of future neuroprosthetic technology and our understanding of motor control in the context of SCI.
-
- Neuroscience
Mice can generate a cognitive map of an environment based on self-motion signals when there is a fixed association between their starting point and the location of their goal.
