Presentation Details
Impact of Aging and Apolipoprotein E4 on Mitral Cells in the Mouse Olfactory Bulb

Dan Zhao, Syed Islam, Shaolin Liu, .

University of Georgia, Athens, GA, USA

Abstract


Mice with the knockin (KI) human gene encoding the apolipoprotein E4 (APOE4), the strongest genetic risk factor for the late onset Alzheimer’s disease (AD), exhibit age-dependent network dysfunction in the olfactory bulb (OB) and its downstream structure the piriform cortex, indicating that the OB output is subject to influence of two AD risk factors - aging and APOE4 gene. However, the mechanisms at the cellular level remains unclear. In this study, the in vivo multi-channel extracellular recording approach was utilized to compare the OB network oscillatory activities and spontaneous spiking of mitral cells (MC), the principal OB output neurons, between control and APOE4 KI mice at the age of 120 weeks in anesthetized conditions whereas whole cell patch clamp recordings were carried out to assess the neuronal excitability and synaptic activities in MCs in OB slices. We found much fewer actively spiking units and altered oscillation power in recordings from APOE4 KI mice compared to their age- and sex-matched control animals. Consistently, MCs in OB slices prepared from APOE4 KI mice showed a significantly lower level of spontaneous firing activities and altered action potential parameters compared to control animals, indicating detrimental effects of APOE4 on MC excitability. Interestingly, MCs in OB slices from APOE4 KI mice also exhibited a reduced level of spontaneous inhibitory postsynaptic currents, suggesting an altered interaction between excitatory and inhibitory local neurons as well as the related networks. To determine whether these APOE4 effects are age-dependent, we will extend these studies to adult (~25 weeks) mice. Taken together, our findings demonstrate the detrimental actions of APOE4 on the principal OB output neurons and related network operation in aged mice.

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