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 is available at: https://datashare.ed.ac.uk/handle/10283/4774Source data and code is available at https://github.com/MattNolanLab/lec_to_mec.
Fan cells in lateral entorhinal cortex directly influence medial entorhinal cortex through synaptic connections in layer 1https://doi.org/10.7488/ds/3787.
- Matthew F Nolan
- 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.
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.
- Lisa Giocomo, Stanford School of Medicine, United States
© 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.
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