RT Journal Article SR Electronic T1 Prefrontal, striatal, and VTA subnetwork dynamics during novelty and exploration JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.11.24.469851 DO 10.1101/2021.11.24.469851 A1 Adam J.O. Dede A1 Nader Marzban A1 Ashutosh Mishra A1 Robert Reichert A1 Paul M. Anderson A1 Michael X Cohen YR 2021 UL http://biorxiv.org/content/early/2021/11/25/2021.11.24.469851.abstract AB Multiple distinct brain areas have been implicated in memory including the prefrontal cortex (PFC), striatum (STR), and ventral tegmental area (VTA). Information-exchange across these widespread networks requires flexible coordination at a fine time-scale. In the present study, we collected high-density recordings from the PFC, STR, and VTA of male rats during baseline, encoding, consolidation, and retrieval stages of memory formation. Novel sub-regional clustering analyses identified patterns of spatially restricted, temporally coherent, and frequency specific signals that were reproducible across days and were modulated by behavioral states. Clustering identified miniscule patches of neural tissue. Generalized eigen decomposition (GED) reduced each cluster to a single time series. Amplitude envelope correlation of the cluster time series was used to assess functional connectivity between clusters. Dense intra- and inter regional functional connectivity characterized the baseline period, with delta oscillations playing an outsized role. There was a dramatic pruning of network connectivity during encoding. Connectivity rebounded during consolidation, but connections in the theta band became stronger, and those in the delta band were weaker. Finally, during retrieval, connections were not as severely reduced as they had been during encoding, and specifically theta and higher-frequency connections were stronger. Underlying these connectivity changes, the anatomical extent of clusters observed in the gamma band in the PFC and in both the gamma and delta bands in the VTA changed markedly across behavioral conditions. These results demonstrate the brain’s ability to reorganize functionally at both the intra- and inter-regional levels during different stages of memory processing.SIGNIFICANCE STATEMENT The brain is often thought of as a mosaic of areas each with static functions that activate or deactivate with task demands. Here, we used large-scale recordings (196 simultaneous electrodes) and developed a multivariate analysis approach to analyze data from all our recording locations simultaneously. This analysis revealed that the brain dramatically reorganized itself at both local and long-distance spatial scales during different stages of memory processing. These results demonstrate an extreme degree of flexibility in functional anatomy. Rather than thinking about the brain as a set of static mosaic tiles, it may better be characterized as a quickly moldable piece of clay where each part’s function changes as the whole is reshaped from moment to moment.Competing Interest StatementThe authors have declared no competing interest.