Oligomeric amyloid-β peptide disrupts olfactory information output by impairment of local inhibitory circuits in rat olfactory bulb

Although early olfactory dysfunction has been found in patients with Alzheimer's disease, the under-lying mechanisms remain unclear. In this study, we investigated whether and how oligomeric amyloid-beta peptide (A beta) affects the responses of mitral cells (MCs). We found that oligomeric A beta 1-42 increased spontaneous and evoked firing rates but decreased the ratio of evoked to spontaneous firings in MCs. A beta 1-42 oligomers showed no impact on the hyperactivity exerted by pharmacological blockage of GABA(A) receptors, suggesting an involvement of GABAergic inhibitory transmission in A beta 1 to 42-einduced over-excitability. It was further determined that A beta 1-42 oligomers inhibited the frequency of spontaneous inhibitory postsynaptic currents and miniature inhibitory postsynaptic currents, as well as the amplitude of miniature inhibitory postsynaptic currents in MCs. Both recurrent and lateral inhibition of MCs, which are critical for odor discrimination, were also disrupted by A beta 1-42 oligomers. The above data indicate that A beta impairs local inhibitory circuits and thereby leads to perturbations of olfactory information output in the olfactory bulb. This study reveals a cellular and synaptic basis of olfactory deficits associated with Alzheimer's disease. (C) 2016 Elsevier Inc. All rights reserved.