Explaining heterogeneity in medial entorhinal cortex with task-driven neural networks

Aran Nayebi, Alexander Attinger, Malcolm G. Campbell, Kiah Hardcastle, Isabel I.C. Low, Caitlin S. Mallory, Gabriel C. Mel, Ben Sorscher, Alex H. Williams, Surya Ganguli, Lisa M. Giocomo, Daniel L.K. Yamins

Research output: Chapter in Book/Report/Conference proceedingConference contribution


Medial entorhinal cortex (MEC) supports a wide range of navigational and memory related behaviors. Well-known experimental results have revealed specialized cell types in MEC - e.g. grid, border, and head-direction cells - whose highly stereotypical response profiles are suggestive of the role they might play in supporting MEC functionality. However, the majority of MEC neurons do not exhibit stereotypical firing patterns. How should the response profiles of these more “heterogeneous” cells be described, and how do they contribute to behavior? In this work, we took a computational approach to addressing these questions. We first performed a statistical analysis that shows that heterogeneous MEC cells are just as reliable in their response patterns as the more stereotypical cell types, suggesting that they have a coherent functional role. Next, we evaluated a spectrum of candidate models in terms of their ability to describe the response profiles of both stereotypical and heterogeneous MEC cells. We found that recently developed task-optimized neural network models are substantially better than traditional grid cell-centric models at matching most MEC neuronal response profiles - including those of grid cells themselves - despite not being explicitly trained for this purpose. Specific choices of network architecture (such as gated nonlinearities and an explicit intermediate place cell representation) have an important effect on the ability of the model to generalize to novel scenarios, with the best of these models closely approaching the noise ceiling of the data itself. We then performed in silico experiments on this model to address questions involving the relative functional relevance of various cell types, finding that heterogeneous cells are likely to be just as involved in downstream functional outcomes (such as path integration) as grid and border cells. Finally, inspired by recent data showing that, going beyond their spatial response selectivity, MEC cells are also responsive to non-spatial rewards, we introduce a new MEC model that performs reward-modulated path integration. We find that this unified model matches neural recordings across all variable-reward conditions. Taken together, our results point toward a conceptually principled goal-driven modeling approach for moving future experimental and computational efforts beyond overly-simplistic single-cell stereotypes.

Original languageEnglish (US)
Title of host publicationAdvances in Neural Information Processing Systems 34 - 35th Conference on Neural Information Processing Systems, NeurIPS 2021
EditorsMarc'Aurelio Ranzato, Alina Beygelzimer, Yann Dauphin, Percy S. Liang, Jenn Wortman Vaughan
PublisherNeural information processing systems foundation
Number of pages13
ISBN (Electronic)9781713845393
StatePublished - 2021
Event35th Conference on Neural Information Processing Systems, NeurIPS 2021 - Virtual, Online
Duration: Dec 6 2021Dec 14 2021

Publication series

NameAdvances in Neural Information Processing Systems
ISSN (Print)1049-5258


Conference35th Conference on Neural Information Processing Systems, NeurIPS 2021
CityVirtual, Online

ASJC Scopus subject areas

  • Computer Networks and Communications
  • Information Systems
  • Signal Processing


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