# The effects of amyloidosis and aging on glutamatergic and GABAergic synapses, and interneurons in the barrel cortex and non-neocortical brain regions

## TL;DR

This study explores how amyloidosis and aging affect synapses and interneurons in brain regions crucial for Alzheimer's disease progression.

## Contribution

The study extends previous findings on excitation/inhibition balance to non-neocortical brain regions in Alzheimer's and aging mouse models.

## Key findings

- Amyloidosis disrupts excitatory synapse alignment and reduces synapses and SST cells but not PV cells.
- Aging reduces synapses, I/E ratios, and both SST and PV cells across multiple brain regions.
- Aging has a stronger impact on Pir, BMA, and DM regions compared to amyloidosis.

## Abstract

Previous studies on changes in the distribution of GABAergic interneurons and excitation/inhibition (E/I) balance in Alzheimer’s disease (AD) and aging were mainly conducted in the neocortex and hippocampus. However, the limbic system is the primary and crucial location for AD progression. Therefore, in this study, we utilized AD and aging mouse models to investigate the E/I balance and the distribution of parvalbumin (PV)- and somatostatin (SST)-expressing cells in S1BF (barrel field of primary somatosensory cortex, barrel cortex), CA1 hippocampal area and brain regions beyond the neocortex and hippocampus, including retrosplenial cortex (RSC, which is composed of RSG and RSA), piriform cortex (Pir), amygdala (BMA), and hypothalamus (DM). We discovered that amyloidosis may disrupt the alignment of excitatory pre- and postsynaptic quantities. Amyloidosis reduces the quantity of synapses and SST cells, but does not impact the counts of PV cells. By contrast, aging is linked to a decline in synapses, I/E ratios, SST and PV cells. Amyloidosis affects the S1BF and BMA, while aging may harm all studied regions, including the S1BF, RSC, hippocampus, Pir, BMA, and DM. Aging mostly affects synapses and I/E ratios in Pir, BMA, and DM, and PV and SST interneurons in the hippocampus.