Optogenetic disruption of neural dynamics in the prefrontal cortex impaired spatial learning

Abstract

1.Cortical neural activity is highly dynamical at several temporal scales, property that has been postulated to be critical for the emergence of specific patterns supporting cognitive operations. During spatial learning, task-associated activity patterns gradually develop in the medial prefrontal cortex (mPFC) as the subject acquires experience. If neural activity dynamics is required in the mPFC for spatial learning is still unclear. Here we show that optogenetic entrainment of neural activity the mPFC disrupted local oscillatory and single-neuron dynamics. When applied during spatial training, optogenetic entrainment impaired behavioral performance and navigation strategy progression, a hallmark of spatial learning supported by the mPFC. Also, optogenetic entrainment blocked the emergence of learning-related activity patterns such as cross-frequency coupling and firing patterns signaling efficient goal approaching. Importantly, during memory retrieval, training-stimulated mice showed impaired performance in the absence of optogenetic stimulation. This evidence show that neural activity dynamics in the mPFC is crucial for spatial learning. SignificanceCortical neural activity is highly fluctuating at several temporal scales, which has been postulated to be critical for cognitive functions. The medial prefrontal cortex (mPFC) is involved in the learning-related optimization of behavioral responses; however, it is unknown whether the dynamics of neural activity in the mPFC is required for learning. Here we found that optogenetic disruption of ongoing neural activity dynamics in the mPFC during training in a spatial memory acquisition task impaired spatial learning and hindered the emergence of learning-related activity patterns. These findings provide insight into the role of prefrontal activity dynamics in cognitive functions.