Modulation of intercolumnar synchronization by endogenous electric fields in cerebral cortex.

Neurons synaptically interacting in a conductive medium generate extracellular endogenous electric fields (EFs) that reciprocally affect membrane potential. Exogenous EFs modulate neuronal activity, and their clinical applications are being profusely explored. However, whether endogenous EFs contribute to network synchronization remains unclear. We analyzed spontaneously generated slow-wave activity in the cerebral cortex network in vitro, which allowed us to distinguish synaptic from nonsynaptic mechanisms of activity propagation and synchronization. Slow oscillations generated EFs that propagated independently of synaptic transmission. We demonstrate that cortical oscillations modulate spontaneous rhythmic activity of neighboring synaptically disconnected cortical columns if layers are aligned. We provide experimental evidence that these EF-mediated effects are compatible with electric dipoles. With a model of interacting dipoles, we reproduce the experimental measurements and predict that endogenous EF-mediated synchronizing effects should be relevant in the brain. Thus, experiments and models suggest that electric-dipole interactions contribute to synchronization of neighboring cortical columns.

Modulation of cortical slow oscillations and complexity across anesthesia levels.

The ability of different groups of cortical neurons to engage in causal interactions that are at once differentiated and integrated results in complex dynamic patterns. Complexity is low during periods of unconsciousness (deep sleep, anesthesia, unresponsive wakefulness syndrome) in which the brain tends to generate a stereotypical pattern consisting of alternating active and silent periods of neural activity-slow oscillations- and is high during wakefulness. But how is cortical complexity built up? Is it a continuum? An open question is whether cortical complexity can vary within the same brain state. Here we recorded with 32-channel multielectrode arrays from the cortical surface of the mouse and used both spontaneous dynamics (wave propagation entropy and functional complexity) and a perturbational approach (a variation of the perturbation complexity index) to measure complexity at different anesthesia levels. Variations in anesthesia level within the bistable regime of slow oscillations (0.1-1.5 Hz) resulted in a modulation of the slow oscillation frequency. Both perturbational and spontaneous complexity increased with decreasing anesthesia levels, in correlation with the decrease in coherence of the underlying network. Changes in complexity level are related to, but not dependent on, changes in excitability. We conclude that cortical complexity can vary within a single brain state dominated by slow oscillations, building up to the higher complexity associated with consciousness.

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.