Department of Radiology, University of Pittsburgh, McGowan Institute for Regenerative Medicine Building, 3025 E. Carson St., rm. 159, Pittsburgh, PA, 15203, United States.
Department of Radiology, University of Pittsburgh, McGowan Institute for Regenerative Medicine Building, 3025 E. Carson St., rm. 159, Pittsburgh, PA, 15203, United States; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States.
Neuroimage. 2023 Jul 1;274:120121. doi: 10.1016/j.neuroimage.2023.120121. Epub 2023 Apr 18.
Awake rodent fMRI is increasingly common over the use of anesthesia since it permits behavioral paradigms and does not confound normal brain function or neurovascular coupling. It is well established that adequate acclimation to the loud fMRI environment and head fixation reduces stress in the rodents and allows for whole brain imaging with little contamination from motion. However, it is unknown whether high-resolution fMRI with increased susceptibility to motion and lower sensitivity can measure small, but spatially discrete, activations in awake mice. To examine this, we used contrast-enhanced cerebral blood volume-weighted (CBVw) fMRI in the mouse olfactory bulb for its enhanced sensitivity and neural specificity. We determined that activation patterns in the glomerular layer to four different odors were spatially distinct and were consistent with previously established histological patterns. In addition, odor-evoked laminar activations were greatest in superficial layers that decreased with laminar depth, similar to previous observations. Interestingly, the fMRI response strengths in the granule cell layer were greater in awake mice than our previous anesthetized rat studies, suggesting that feedback neural activities were intact with wakefulness. We finally determined that fMRI signal changes to repeated odor exposure (i.e., olfactory adaptation) attenuated relatively more in the feedback granule cell layer compared to the input glomerular layer, which is consistent with prior observations. We, therefore, conclude that high-resolution CBVw fMRI can measure odor-specific activation patterns and distinguish changes in laminar activity of head and body restrained awake mice.
清醒状态下的啮齿类动物 fMRI 越来越普遍地取代了麻醉，因为它允许行为范式，并且不会混淆正常的大脑功能或神经血管耦合。众所周知，充分适应 fMRI 环境和头部固定可以减少啮齿动物的压力，从而可以进行全脑成像，而很少受到运动的影响。然而，尚不清楚高分辨率 fMRI 是否能够测量到清醒小鼠中较小但空间离散的激活。为了研究这个问题，我们使用对比增强脑血流容积加权（CBVw） fMRI 来检测嗅球，因为它具有更高的灵敏度和神经特异性。我们确定了对四种不同气味的肾小球层的激活模式在空间上是不同的，并且与先前建立的组织学模式一致。此外，气味诱发的分层激活在浅层最强烈，随着分层深度的增加而减少，这与以前的观察结果一致。有趣的是，与我们之前的麻醉大鼠研究相比，清醒小鼠的颗粒细胞层的 fMRI 响应强度更大，这表明反馈神经活动在清醒时是完整的。我们最后确定，与输入的肾小球层相比，重复气味暴露（即嗅觉适应）引起的 fMRI 信号变化在反馈颗粒细胞层中相对减弱更多，这与之前的观察结果一致。因此，我们得出结论，高分辨率 CBVw fMRI 可以测量特定气味的激活模式，并区分头部和身体约束的清醒小鼠的分层活动变化。
