Neuroscience Bulletin

, Volume 28, Issue 5, pp 585–594 | Cite as

Amyloid-β depresses excitatory cholinergic synaptic transmission in Drosophila

Original Article

Abstract

Objective

Decline, disruption, or alterations of nicotinic cholinergic mechanisms contribute to cognitive dysfunctions like Alzheimer’s disease (AD). Although amyloid-β (Aβ) aggregation is a pathological hallmark of AD, the mechanisms by which Aβ peptides modulate cholinergic synaptic transmission and memory loss remain obscure. This study was aimed to investigate the potential synaptic modulation by Aβ of the cholinergic synapses between olfactory receptor neurons and projection neurons (PNs) in the olfactory lobe of the fruit fly.

Methods

Cholinergic spontaneous and miniature excitatory postsynaptic current (mEPSC) were recorded with whole-cell patch clamp from PNs in Drosophila AD models expressing Aβ40, Aβ42, or Aβ42Arc peptides in neural tissue.

Results

In fly pupae (2 days before eclosion), overexpression of Aβ42 or Aβ42Arc, but not Aβ40, led to a significant decrease of mEPSC frequency, while overexpression of Aβ40, Aβ42, or Aβ42Arc had no significant effect on mEPSC amplitude. In contrast, Pavlovian olfactory associative learning and lifespan assays showed that both short-term memory and lifespan were decreased in the Drosophila models expressing Aβ40, Aβ42, or Aβ42Arc.

Conclusion

Both electrophysiological and behavioral results showed an effect of Aβ peptide on cholinergic synaptic transmission and suggest a possible mechanism by which Aβ peptides cause cholinergic neuron degeneration and the consequent memory loss.

Keywords

Aβ peptide projection neurons Alzheimer’s disease neurotoxicity electrophysiolgy cholinergic synaptic transmission 

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Copyright information

© Shanghai Institutes for Biological Sciences, CAS and Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Department of Anatomy and Neurobiology, Zhongshan School of MedicineSun Yat-sen UniversityGuangzhouChina
  2. 2.Department of Neurologythe Fourth Affiliated Hospital of Harbin Medical UniversityHarbinChina
  3. 3.Department of Neurologythe Second Affiliated Hospital of Harbin Medical UniversityHarbinChina

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