Complex Propagation Patterns Characterize Human Cortical Activity during Slow-Wave Sleep

Cortical electrical activity during nonrapid eye movement (non-REM) sleep is dominated by slow-wave activity (SWA). At larger spatial scales (similar to 2-30 cm), investigated by scalp EEG recordings, SWA has been shown to propagate globally over wide cortical regions as traveling waves, which has been proposed to serve as a temporal framework for neural plasticity. However, whether SWA dynamics at finer spatial scales also reflects the orderly propagation has not previously been investigated in humans. To reveal the local, finer spatial scale (similar to 1-6 cm) patterns of SWA propagation during non-REM sleep, electrocorticographic (ECoG) recordings were conducted from subdurally implanted electrode grids and a nonlinear correlation technique [mutual information (MI)] was implemented. MI analysis revealed spatial maps of correlations between cortical areas demonstrating SWA propagation directions, speed, and association strength. Highest correlations, indicating significant coupling, were detected during the initial positive-going deflection of slow waves. SWA propagated predominantly between adjacent cortical areas, albeit spatial noncontinuities were also frequently observed. MI analysis further uncovered significant convergence and divergence patterns. Areas receiving the most convergent activity were similar to those with high divergence rate, while reciprocal and circular propagation of SWA was also frequent. We hypothesize that SWA is characterized by distinct attributes depending on the spatial scale observed. At larger spatial scales, the orderly SWA propagation dominates; at the finer scale of the ECoG recordings, non-REM sleep is characterized by complex SWA propagation patterns

Astrocytes convert network excitation to tonic inhibition of neurons

<p>Abstract</p> <p>Background</p> <p>Glutamate and γ-aminobutyric acid (GABA) transporters play important roles in balancing excitatory and inhibitory signals in the brain. Increasing evidence suggest that they may act concertedly to regulate extracellular levels of the neurotransmitters.</p> <p>Results</p> <p>Here we present evidence that glutamate uptake-induced release of GABA from astrocytes has a direct impact on the excitability of pyramidal neurons in the hippocampus. We demonstrate that GABA, synthesized from the polyamine putrescine, is released from astrocytes by the reverse action of glial GABA transporter (GAT) subtypes GAT-2 or GAT-3. GABA release can be prevented by blocking glutamate uptake with the non-transportable inhibitor DHK, confirming that it is the glutamate transporter activity that triggers the reversal of GABA transporters, conceivably by elevating the intracellular Na⁺concentration in astrocytes. The released GABA significantly contributes to the tonic inhibition of neurons in a network activity-dependent manner. Blockade of the Glu/GABA exchange mechanism increases the duration of seizure-like events in the low-[Mg²⁺] <it>in vitro </it>model of epilepsy. Under <it>in vivo </it>conditions the increased GABA release modulates the power of gamma range oscillation in the CA1 region, suggesting that the Glu/GABA exchange mechanism is also functioning in the intact hippocampus under physiological conditions.</p> <p>Conclusions</p> <p>The results suggest the existence of a novel molecular mechanism by which astrocytes transform glutamat<it>ergic </it>excitation into GABA<it>ergic </it>inhibition providing an adjustable, <it>in situ </it>negative feedback on the excitability of neurons.</p

Single-neuron dynamics in human focal epilepsy

Epileptic seizures are traditionally characterized as the ultimate expression of monolithic, hypersynchronous neuronal activity arising from unbalanced runaway excitation. Here we report the first examination of spike train patterns in large ensembles of single neurons during seizures in persons with epilepsy. Contrary to the traditional view, neuronal spiking activity during seizure initiation and spread was highly heterogeneous, not hypersynchronous, suggesting complex interactions among different neuronal groups even at the spatial scale of small cortical patches. In contrast to earlier stages, seizure termination is a nearly homogenous phenomenon followed by an almost complete cessation of spiking across recorded neuronal ensembles. Notably, even neurons outside the region of seizure onset showed significant changes in activity minutes before the seizure. These findings suggest a revision of current thinking about seizure mechanisms and point to the possibility of seizure prevention based on spiking activity in neocortical neurons