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Abstract Cortical network undergoes rewiring everyday due to learning and memory events. To investigate the trends of population adaptation in neocortex overtime, we record cellular activity of large-scale cortical populations in response to neutral environments and conditioned contexts and identify a general intrinsic cortical adaptation mechanism, naming rectified activity-dependent population plasticity (RAPP). Comparing each adjacent day, the previously activated neurons reduce activity, but remain with residual potentiation, and increase population variability in proportion to their activity during previous recall trials. RAPP predicts both the decay of context-induced activity patterns and the emergence of sparse memory traces. Simulation analysis reveal that the local inhibitory connections might account for the residual potentiation in RAPP. Intriguingly, introducing the RAPP phenomenon in the artificial neural network show promising improvement in small sample size pattern recognition tasks. Thus, RAPP represents a phenomenon of cortical adaptation, contributing to the emergence of long-lasting memory and high cognitive functions.

Abstract Memory engrams are a subset of learning activated neurons critical for memory recall, consolidation, extinction and separation. While the transcriptional profile of engrams after learning suggests profound neural changes underlying plasticity and memory formation, little is known about how memory engrams are selected and allocated. As epigenetic factors suppress memory formation, we developed a CRISPR screening in the hippocampus to search for factors controlling engram formation. We identified histone lysine-specific demethylase 4a (Kdm4a) as a negative regulator for engram formation. Kdm4a is downregulated after neural activation and controls the volume of mossy fiber boutons. Mechanistically, Kdm4a anchors to the exonic region of Trpm7 gene loci, causing the stalling of nascent RNAs and allowing burst transcription of Trpm7 upon the dismissal of Kdm4a. Furthermore, the YTH domain containing protein 2 (Ythdc2) recruits Kdm4a to the Trpm7 gene and stabilizes nascent RNAs. Reducing the expression of Kdm4a in the hippocampus via genetic manipulation or artificial neural activation facilitated the ability of pattern separation in rodents. Our work indicates that Kdm4a is a negative regulator of engram formation and suggests a priming state to generate a separate memory.

Hippocampal lesioned mice form new memories. Here, the authors show the lateral entorhinal cortex modulates learning-induced cortical long-range gamma synchrony in a hippocampal-dependent manner and artificially induced cortical gamma synchrony across cortical areas improved memory encoding in hippocampal lesioned mice.

High-resolution functional 2-photon microscopy of neural activity is a cornerstone technique in current neuroscience, enabling, for instance, the image-based analysis of relations of the organization of local neuron populations and their temporal neural activity patterns. Interpreting local image intensity as a direct quantitative measure of neural activity presumes, however, a consistent within- and across-image relationship between the image intensity and neural activity, which may be subject to interference by illumination artifacts. In particular, the so-called vignetting artifact—the decrease of image intensity toward the edges of an image—is, at the moment, widely neglected in the context of functional microscopy analyses of neural activity, but potentially introduces a substantial center-periphery bias of derived functional measures. In the present report, we propose a straightforward protocol for single image-based vignetting correction. Using immediate-early gene-based 2-photon microscopic neural image data of the mouse brain, we show the necessity of correcting both image brightness and contrast to improve within- and across-image intensity consistency and demonstrate the plausibility of the resulting functional data.