Behavioral and Cellular Tagging in Young and in Early Cognitive Aging.

Alexandra Gros,Victoria Hohendorf,Thomas John Mchugh,Nicole White,Amos W H Lim,Michael Eckert,Szu-Han Wang

doi:10.3389/fnagi.2022.809879

Abstract

The ability to maintain relevant information on a daily basis is negatively impacted by aging. However, the neuronal mechanism manifesting memory persistence in young animals and memory decline in early aging is not fully understood. A novel event, when introduced around encoding of an everyday memory task, can facilitate memory persistence in young age but not in early aging. Here, we investigated in male rats how sub-regions of the hippocampus are involved in memory representation in behavioral tagging and how early aging affects such representation by combining behavioral training in appetitive delayed-matching-to-place tasks with the “cellular compartment analysis of temporal activity by fluorescence in situ hybridization” technique. We show that neuronal assemblies activated by memory encoding were also partially activated by novelty, particularly in the distal CA1 and proximal CA3 subregions in young male rats. In early aging, both encoding- and novelty-triggered neuronal populations were significantly reduced with a more profound effect in encoding neurons. Thus, memory persistence through novelty facilitation engages overlapping hippocampal assemblies as a key cellular signature, and cognitive aging is associated with underlying reduction in neuronal activation.

Highlights

Memory decline is commonly studied at a later stage of aging (>20 months old in rodents, Kausler, 1994; Bettio et al, 2017), while how memory is affected at midlife remains relatively understudied
We showed that behavioral tagging involves a shared hippocampal neuronal assembly in distal CA1 and proximal CA3, and early aging leads to significant reduction of activated neuronal populations that are associated with memory decline
We first examined whether prior training in the Appetitive delayed-matching-to-place (ADMP) task would or would not change the level of immediate early genes (IEGs) expression triggered by the exploration of a novel box, a procedure commonly used in catFISH studies (Guzowski et al, 1999; Vazdarjanova et al, 2002)

Summary

Introduction

Memory decline is commonly studied at a later stage of aging (>20 months old in rodents, Kausler, 1994; Bettio et al, 2017), while how memory is affected at midlife remains relatively understudied. Environmental novelty (i.e., a memory-modulating event), when introduced around memory encoding, can modulate memory persistence (Moncada and Viola, 2007; Ballarini et al, 2009; Wang et al, 2010; Gros and Wang, 2018), upregulate the expression of immediate early genes (IEGs) (Guzowski and Worley, 2001), and induce the expression of plasticity-related proteins. Behavioral tagging provides a robust method to sustain everyday memories (Wang et al, 2010; Nonaka et al, 2017) This strategy is, ineffective to maintain memory persistence in early aging (Gros and Wang, 2018), and the cellular correlates of behavioral tagging in cognitive aging need to be investigated

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