Precise Genome Engineering Center, School of Life Sciences, Guangzhou University, Guangzhou, China.
School of Life Sciences, South China Normal University, Guangzhou, China.
J Alzheimers Dis. 2022;90(3):1277-1289. doi: 10.3233/JAD-220694.
Olfactory decline is an indicator of early-stage Alzheimer's disease (AD). Although the anterior piriform cortex (aPC) is an important brain area involved in processing olfactory input, little is known about how its neuronal activity is affected in early-stage AD.
To elucidate whether odor-induced electrophysiological responses are altered in the aPC of 3-5-month-old APP/PS1 mice.
Using head-fixed multi-channel recording techniques in APP/PS1 AD mouse model to uncover potential aberrance of the aPC neuronal firing and local field potential (LFP) in response to vanillin.
We show that the firing rate of aPC neurons evoked by vanillin is significantly reduced in conscious APP/PS1 mice. LFP analysis demonstrates reduced low- and high-gamma (γlow,γhigh) oscillations during both the baseline and odor stimulation periods in APP/PS1 mice. Moreover, according to spike-field coherence (SFC) analysis, APP/PS1 mice show decreased coherence between odor-evoked spikes and γlow rhythms, while the coherence with γhigh rhythms and the ΔSFC of the oscillations is unaffected. Furthermore, APP/PS1 mice show reduced phase-locking strength in the baseline period, such that there is no difference between baseline and odor-stimulation conditions. This contrasts markedly with wild type mice, where phase-locking strength decreases on stimulation.
The abnormalities in both the neuronal and oscillatory activities of the aPC may serve as electrophysiological indicators of underlying olfactory decline in early AD.
嗅觉减退是早期阿尔茨海默病(AD)的一个指标。虽然前梨状皮层(aPC)是一个参与处理嗅觉输入的重要脑区,但对于其神经元活动在早期 AD 中是如何受到影响的,知之甚少。
阐明在 3-5 个月大的 APP/PS1 小鼠的 aPC 中,气味诱导的电生理反应是否发生改变。
使用 APP/PS1 AD 小鼠模型中的头固定多通道记录技术,揭示 aPC 神经元在香草醛刺激下放电和局部场电位(LFP)的潜在异常。
我们发现,在清醒的 APP/PS1 小鼠中,香草醛诱发的 aPC 神经元的放电率显著降低。LFP 分析表明,在 APP/PS1 小鼠中,基线和气味刺激期间的低γ(γlow)和高γ(γhigh)振荡均减少。此外,根据尖峰-场相干性(SFC)分析,APP/PS1 小鼠显示出气味诱发的尖峰与 γlow 节律之间的相干性降低,而与 γhigh 节律的相干性和振荡的ΔSFC 不受影响。此外,APP/PS1 小鼠在基线期的相位锁定强度降低,使得基线期和气味刺激条件之间没有差异。这与野生型小鼠形成鲜明对比,在野生型小鼠中,刺激时相位锁定强度降低。
aPC 的神经元和振荡活动的异常可能作为早期 AD 中潜在嗅觉减退的电生理指标。