CELLULAR PROPERTIES OF PIRIFORM CORTEX NEURONS PROGRESSIVELY CHANGE IN HEALTHY RATS TREATED ONCE WITH OLIGOMERIC AMYLOID-BETA (1-42)

Alzheimer's disease (AD) is a neurodegenerative disease and the most common cause of dementia. Olfactory deficits are commonly observed in AD and may serve as early preclinical marker for neurodegenerative diseases including AD (doi: 10.1016/B978-0-444-63855-7.00020-4, 10.3389/fnins.2024.1309482). Amyloidosis mediated by amyloid-beta(1-42) is one key factor in the pathophysiology of AD. Until now most details on mechanisms behind olfactory dysfunction in AD are still unclear. Applying one intracerebral application of oligomeric amyloid-beta(1-42) to healthy adult rodents results in acute and long-term impairments in hippocampal information processing and storage (doi: 10.3389/fnbeh.2015.00103, 10.3389/fnagi.2024.1397901).
Effects of this treatment on the olfactory cortex including the piriform cortex (PCx) are unclear and were tested using whole cell recordings in vitro. Active and passive properties of PCx superficial pyramidal cells were examined at specific time points up to 6 months after a single intracerebral application of oligomeric amyloid-beta(1-42) to the lateral cerebral ventricles of healthy adult male rats. Control animals received a scrambled version of the same peptide.
A progressive decline in input resistance, accompanied by an increase in membrane time constant in PCx neurons, became evident after amyloid-beta treatment. In addition, action potential firing frequency differed in amyloid-beta and control PCx neurons.
Our findings indicate that a single intracerebral inoculation with oligomeric amyloid-beta(1-42) progressively alters passive properties of PCx neurons. This may alter information relay from PCx to other brain areas and thus contribute to the vulnerability of structures such as lateral entorhinal cortex and hippocampus to amyloidosis.
Supported by the Deutsche Forschungsgemeinschaft (SFB874/B1, project number: 122679504).