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Related Experiment Video

Updated: Jun 28, 2025

Preparation of Parasagittal Slices for the Investigation of Dorsal-ventral Organization of the Rodent Medial Entorhinal Cortex
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Spatial Coding Dysfunction and Network Instability in the Aging Medial Entorhinal Cortex.

Charlotte S Herber1,2, Karishma J B Pratt3,4, Jeremy M Shea3,4

  • 1Department of Neurobiology, Stanford University School of Medicine, Stanford, CA, 94305, USA.

Biorxiv : the Preprint Server for Biology
|April 25, 2024
PubMed
Summary
This summary is machine-generated.

Aging impairs spatial memory by destabilizing neural network function in the medial entorhinal cortex (MEC). This age-related decline in spatial coding is linked to altered gene expression in MEC interneurons.

Keywords:
Aginggrid cellmedial entorhinal cortexspatial memorytranscriptomics

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Area of Science:

  • Neuroscience
  • Aging Research
  • Cognitive Neuroscience

Background:

  • Spatial memory, crucial for navigation, declines with age across species.
  • This decline may stem from changes in the hippocampus and medial entorhinal cortex (MEC).
  • The precise impact of aging on cellular and network-level spatial coding within the MEC remains unclear.

Purpose of the Study:

  • To investigate the integrity of spatial coding in the aged medial entorhinal cortex (MEC).
  • To identify molecular and network changes associated with age-related spatial memory deficits.

Main Methods:

  • Utilized in vivo electrophysiology in young, middle-aged, and aged mice navigating virtual environments.
  • Assessed grid cell firing patterns and stability.
  • Performed transcriptomic analysis of MEC tissue from aged mice.

Main Results:

  • Aged grid cells exhibited impaired stabilization of context-specific spatial firing, correlating with memory deficits.
  • Aged MEC networks showed unstable firing patterns, with poor alignment to environmental context changes.
  • Identified 458 differentially expressed genes in aged MEC, with 61 correlated to spatial firing stability, enriched in interneurons and synaptic transmission pathways.

Conclusions:

  • Aging disrupts spatial coding integrity at both cellular and network levels within the medial entorhinal cortex.
  • Transcriptomic alterations, particularly in interneurons, are associated with impaired spatial firing stability and memory deficits in aging.
  • These findings highlight coordinated molecular, cellular, and network mechanisms underlying age-related spatial memory decline.