Grid Cell Firing Pattern Degradation and Path Integration Errors in Aging: Single-Unit Recordings in the Entorhinal Cortex of Young and Aged Fischer 344 Rats

This study investigates age-related degradation of entorhinal cortex grid cell spatial periodicity, firing field regularity, and path integration accuracy in young versus aged Fischer 344 rats on open-field and maze navigation tasks within the context of systems neuroscience and cognitive aging, an area of growing scientific importance given its implications for MEC-targeted intervention assessment for spatial navigation in aging, grid cell-based Alzheimer biomarker research, and attractor network computational model validation. Using chronic tetrode recording in MEC during 20-min open-field sessions, spike sorting, grid score computation (rotational correlation), firing field size and spacing analysis, and path integration accuracy on linear track with variable reward location task, we examine age-related reduction in persistent Na+ current and reduced lateral inhibition in MEC stellate cells degrading attractor network dynamics that generate hexagonally symmetric grid fields, producing lower grid score, enlarged fields, and reduced inter-field spacing regularity — impairing downstream hippocampal spatial coding and path integration in 16 young (4-6 months) and 16 aged (22-24 months) male Fischer 344 rats with MEC tetrode implants, 284 well-isolated single units (168 young, 116 aged) including 84 grid cells (52 young, 32 aged) drawn from Pacific Neuroscience Institute rodent behavioral facility with 1 m x 1 m open field, 2.4 m linear track, and Axona dacqUSB recording system at 48 kHz. Results indicate that aged rats show significantly reduced mean grid score (0.48 vs. 0.84 in young, p<0.001), enlarged firing fields (184 vs. 84 cm2, p<0.001), and 2.4x higher inter-field spacing CV; path integration error at 180 cm is 28.4 cm in aged vs. 8.4 cm in young (3.4x, p<0.001) (p < 0.001), with grid score 0.48 vs. 0.84; field size 184 vs. 84 cm2; path integration error 3.4x larger in aged as the primary quantitative benchmark. Concordance between primary and confirmatory measurement approaches exceeded 93%, validating the analytical framework. These findings contribute empirically to systems neuroscience and cognitive aging and carry actionable implications for the design of programs and policies targeting MEC-targeted intervention assessment for spatial navigation in aging, grid cell-based Alzheimer biomarker research, and attractor network computational model validation.