Ramirez-Gordillo Daniel, Bayer K Ulrich, Restrepo Diego
Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Neuroscience Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
eNeuro. 2022 Sep 20;9(5). doi: 10.1523/ENEURO.0259-22.2022.
Learning and memory requires coordinated activity between different regions of the brain. Here we studied the interaction between infralimbic medial prefrontal cortex (mPFC) and hippocampal dorsal CA1 during associative odorant discrimination learning in the mouse. We found that as the animal learns to discriminate odorants in a go-no go task, the coupling of high frequency neural oscillations to the phase of theta oscillations (theta-referenced phase-amplitude coupling or tPAC) changes in a manner that results in divergence between rewarded and unrewarded odorant-elicited changes in the theta-phase referenced power (tPRP) for beta and gamma oscillations. In addition, in the proficient animal there was a decrease in the coordinated oscillatory activity between CA1 and mPFC in the presence of the unrewarded odorant. Furthermore, the changes in tPAC resulted in a marked increase in the accuracy for decoding contextual odorant identity from tPRP when the animal became proficient. Finally, we studied the role of Ca/calmodulin-dependent protein kinase II α (CaMKIIα), a protein involved in learning and memory, in oscillatory neural processing in this task. We find that the accuracy for decoding the contextual odorant identity from tPRP decreases in CaMKIIα knockout mice and that this accuracy correlates with behavioral performance. These results implicate a role for tPAC and CaMKIIα in olfactory go-no go associative learning in the hippocampal-prefrontal circuit.Coupling of neural oscillations within and between hippocampal CA1 and medial prefrontal cortex (mPFC) is involved in spatial learning and memory, but the role of oscillation coupling for other learning tasks is not well understood. Here we performed local field potential recording in CA1 and mPFC in mice learning to differentiate rewarded from unrewarded odorants in an associative learning task. We find that odorant-elicited changes in the power of bursts of gamma oscillations at distinct phases of theta oscillations become divergent as the animal becomes proficient allowing decoding of contextual odorant identity. Finally, we find that the accuracy to decode contextual odorant identity decreases in mice deficient for the expression of Ca/calmodulin-dependent protein kinase II α, a protein involved in synaptic plasticity.
学习和记忆需要大脑不同区域之间的协同活动。在此，我们研究了小鼠在联想性气味辨别学习过程中，腹内侧前额叶皮质（mPFC）的下缘皮质与海马背侧CA1之间的相互作用。我们发现，当动物在“是-否”任务中学习辨别气味时，高频神经振荡与θ振荡相位的耦合（θ参考相位-振幅耦合或tPAC）会发生变化，导致奖励和未奖励气味诱发的β和γ振荡的θ相位参考功率（tPRP）变化出现差异。此外，在熟练的动物中，未奖励气味出现时，CA1和mPFC之间的协同振荡活动会减少。此外，当动物变得熟练时，tPAC的变化导致从tPRP解码情境气味身份的准确性显著提高。最后，我们研究了钙/钙调蛋白依赖性蛋白激酶IIα（CaMKIIα），一种参与学习和记忆的蛋白质，在该任务的振荡神经处理中的作用。我们发现，在CaMKIIα基因敲除小鼠中，从tPRP解码情境气味身份的准确性降低，且这种准确性与行为表现相关。这些结果表明tPAC和CaMKIIα在海马-前额叶回路的嗅觉“是-否”联想学习中发挥作用。海马CA1和内侧前额叶皮质（mPFC）内部及之间的神经振荡耦合参与空间学习和记忆，但振荡耦合在其他学习任务中的作用尚不清楚。在此，我们对正在联想学习任务中学习区分奖励和未奖励气味的小鼠的CA1和mPFC进行了局部场电位记录。我们发现，随着动物变得熟练，在θ振荡不同相位的γ振荡爆发功率中，气味诱发的变化变得不同，从而能够解码情境气味身份。最后，我们发现，在缺乏参与突触可塑性的钙/钙调蛋白依赖性蛋白激酶IIα表达的小鼠中，解码情境气味身份的准确性降低。
