Control of cortical oscillatory frequency by a closed-loop system

Abstract Background We present a closed-loop system able to control the frequency of slow oscillations (SO) spontaneously generated by the cortical network in vitro. The frequency of SO can be controlled by direct current (DC) electric fields within a certain range. Here we set out to design a system that would be able to autonomously bring the emergent oscillatory activity to a target frequency determined by the experimenter. Methods The cortical activity was recorded through an electrode and was analyzed online. Once a target frequency was set, the frequency of the slow oscillation was steered through the injection of DC of variable intensity that generated electric fields of proportional amplitudes in the brain slice. To achieve such closed-loop control, we designed a custom programmable stimulator ensuring low noise and accurate tuning over low current levels. For data recording and analysis, we relied on commercial acquisition and software tools. Results The result is a flexible and reliable system that ensures control over SO frequency in vitro. The system guarantees artifact removal, minimal gaps in data acquisition and robustness in spite of slice heterogeneity. Conclusions Our tool opens new possibilities for the investigation of dynamics of cortical slow oscillations—an activity pattern that is associated with cognitive processes such as memory consolidation, and that is altered in several neurological conditions—and also for potential applications of this technology

Altered neocortical dynamics in a mouse model of Williams-Beuren syndrome

Williams-Beuren syndrome (WBS) is a rare neurodevelopmental disorder characterized by moderate intellectual disability and learning difficulties alongside behavioral abnormalities such as hypersociability. Several structural and functional brain alterations are characteristic of this syndrome, as well as disturbed sleep and sleeping patterns. However, the detailed physiological mechanisms underlying WBS are mostly unknown. Here, we characterized the cortical dynamics in a mouse model of WBS previously reported to replicate most of the behavioral alterations described in humans. We recorded the laminar local field potential generated in the frontal cortex during deep anesthesia and characterized the properties of the emergent slow oscillation activity. Moreover, we performed micro-electrocorticogram recordings using multielectrode arrays covering the cortical surface of one hemisphere. We found significant differences between the cortical emergent activity and functional connectivity between wild-type mice and WBS model mice. Slow oscillations displayed Up states with diminished firing rate and lower high-frequency content in the gamma range. Lower firing rates were also recorded in the awake WBS animals while performing a marble burying task and could be associated with the decreased spine density and thus synaptic connectivity in this cortical area. We also found an overall increase in functional connectivity between brain areas, reflected in lower clustering and abnormally high integration, especially in the gamma range. These results expand previous findings in humans, suggesting that the cognitive deficits characterizing WBS might be associated with reduced excitability, plus an imbalance in the capacity to functionally integrate and segregate information.This work was supported by EU H2020 Research and Innovation Programme under Grant Agreement No. 720270 (HBP SGA2), BFU2017-85048-R Spanish Ministry of Science and CERCA Programme/Generalitat de Catalunya to MVSV