Poster abstracts
Poster number 81 submitted by Irene Davila Mejia
Microglial Dynamics in Memory Organization and Aging
Irene Davila Mejia (Neuroscience Graduate Program), Abigail Long (Department of Psychology, Ohio State University), Patricia Schneider (Department of Psychology, Ohio State University), Jordan Albrecht, Gavin Hassel (Department of Psychology, Ohio State University), Megha Sehgal (Department of Psychology, Ohio State University)
Abstract:
Normal aging is associated with subtle memory impairments that contribute to an increasing public health burden. Our goal is to identify early behavioral and neural biomarkers of aging-related cognitive decline. The retrosplenial cortex (RSC) is a brain region important for various memory tasks, such as contextual and spatial memory formation, which become vulnerable during aging. Consistent with this, the RSC shows early and selective dysfunction during normal aging and Alzheimer’s Disease. Despite evidence of this vulnerability, cellular and circuit-level mechanisms in the aging RSC remain poorly defined. Here, we test the hypothesis that RSC dysfunction contributes to age-related memory decline. To determine the role of RSC activation in memory processes, we measured neuronal activation during contextual memory retrieval in middle-aged (MA) and young mice. Mice were divided into home cage (HC), novel context exposure (CTX), and contextual fear conditioning (CFC). We quantified neuronal activity during memory recall using cFos immunostaining. Consistent with research showing similar CFC memory performance in young and MA mice, we found no recall differences between groups. Both age groups showed increased neuronal activation following CTX and CFC compared to HC. Aging disrupts synaptic plasticity and circuit remodeling in a microglia-dependent manner, prompting us to study microglial contributions to RSC function during aging. We identified microglia using Iba1 and compared proximity of microglial processes to neurons active during memory recall. We investigated two RSC subregions, the anterior (aRSC) and posterior (pRSC), which have distinct connectivity and memory functions. In the aRSC of young mice, microglia preferentially interacted with cFos-positive cells in HC and CTX groups, but not CFC. In the pRSC, this occurred in CFC but not HC or CTX. MA mice showed different patterns, indicating dysfunction in RSC microglia-neuronal interaction. Specifically, in the aRSC this pattern is seen in the CFC group, but not the HC and CTX groups. In the pRSC this is the case in the HC and CFC groups, but not the CTX group. Our data suggest a task- and subregion-specific microglial interactions with active RSC neurons become dysregulated in middle age, potentially contributing to age-related memory deficits.
Keywords: microglia, memory, aging