Neuronal firing properties in Alzheimer's disease

Neuronal firing properties in Alzheimer's disease

Alzheimer's disease (AD) is the most common form of dementia, affecting an estimated 44.4 million people worldwide in 2013. Symptoms of AD include progressive memory loss, believed to be caused by a build-up of amyloid-β (Aβ) plaques in the Medial Temporal Lobe (MTL). These plaques lead to dysfunction in areas of the MTL, including the hippocampus and the entorhinal cortex (EC), but the molecular mechanisms behind this dysfunction are not well understood.

The EC is made up of medial (MEC) and lateral (LEC) areas associated with spatial and non-spatial memory processing respectively. The neurons from layer II of these regions project to the Dentate Gyrus (DG) in the hippocampus through the medial and lateral perforant pathways (MPP and LPP). Stellate cells (SCs) are the major inputs to the MPP and fan cells (FCs) are the major inputs to the LPP.

Hélène Marie and colleagues at the Institut de Pharmacologie Moléculaire et Cellulaire and the University of Turin studied the electrophysiology of SCs and FCs in wild-type mice and a transgenic AD mouse model (Tg2576). By comparing the firing properties in these cells at an age when the Tg2576 mice began to show symptoms of AD they were able to examine how Aβ build-up affects them.

Interestingly, the researchers found that SCs and FCs were altered differently in Tg2576 mice during early onset of AD symptoms. The SCs were only mildly affected with fast after-hyperpolarisation (fAHP) being significantly increased during sustained tonic firing. However, during maximal stimulation there were no observed differences between wild-type and Tg2576 SC cells. In contrast, FCs of Tg2576 mice had a significantly reduced firing frequency and rheobase compared to wild-type FCs.

These results suggest that spatial information processing from SCs to the hippocampus remains relatively intact during the early stages of AD progression. However, other sensory inputs to the hippocampus, processed by FCs are more likely to be affected.

Both SCs and FCs are important to episodic memory formation. The changes in the firing properties of these cells in Tg2576 mice, likely caused by Aβ build-up, appear to be partially responsible for the symptoms associated with AD.

Slice electrophysiology recordings

For this study brain slices including the EC and hippocampus were visualised under IR-DIC using a Scientifica SliceScope Pro 1000. Electrophysiological recordings were made using a PatchStar manipulator linked to a Muticlamp700B amplifier and DigiData data acquisition hardware with pClamp10 software.

Paper Reference

Marcantoni A., Raymond E.F., Carbone E., Marie H. Firing properties of entorhinal cortex neurons and early alterations in an Alzheimer's disease transgenic model Pflügers Archiv (2014) DOI: 10.1007/s00424-013-1368-z.

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