Consciousness is supported by near-critical cortical electrodynamics

Mounting evidence suggests that during conscious states, the electrodynamics of the cortex are poised near a critical point or phase transition, and that this near-critical behavior supports the vast flow of information through cortical networks during conscious states. Here, for the first time, we empirically identify the specific critical point near which conscious cortical dynamics operate as the edge-of-chaos critical point, or the boundary between stability and chaos. We do so by applying the recently developed modified 0-1 chaos test to electrocorticography (ECoG) and magnetoencephalography (MEG) recordings from the cortices of humans and macaques across normal waking, generalized seizure, GABAergic anesthesia, and psychedelic states. Our evidence suggests that cortical information processing is disrupted during unconscious states because of a transition of cortical dynamics away from this critical point; conversely, we show that psychedelics may increase the information-richness of cortical activity by tuning cortical electrodynamics closer to this critical point. Finally, we analyze clinical electroencephalography (EEG) recordings from patients with disorders of consciousness (DOC), and show that assessing the proximity of cortical electrodynamics to the edge-of-chaos critical point may be clinically useful as a new biomarker of consciousness.

Neuron–Oligodendrocyte Communication in Myelination of Cortical GABAergic Cells

Axonal myelination by oligodendrocytes increases the speed and reliability of action potential propagation, and so plays a pivotal role in cortical information processing. The extent and profile of myelination vary between different cortical layers and groups of neurons. Two subtypes of cortical GABAergic neurons are myelinated: fast-spiking parvalbumin-expressing cells and somatostatin-containing cells. The expression of pre-nodes on the axon of these inhibitory cells before myelination illuminates communication between oligodendrocytes and neurons. We explore the consequences of myelination for action potential propagation, for patterns of neuronal connectivity and for the expression of behavioral plasticity.

Asynchronous Glutamate Release at Autapses Regulates Spike Reliability and Precision in Mouse Neocortical Pyramidal Cells

Autapses are self-synapses of a neuron. Inhibitory autapses in the neocortex release GABA in 2 modes, synchronous release and asynchronous release (AR), providing precise and prolonged self-inhibition, respectively. A subpopulation of neocortical pyramidal cells (PCs) also forms functional autapses, activation of which promotes burst firing by strong unitary autaptic response that reflects synchronous glutamate release. However, it remains unclear whether AR occurs at PC autapses and plays a role in neuronal signaling. We performed whole-cell recordings from layer-5 PCs in slices of mouse prefrontal cortex (PFC). In response to action potential (AP) burst, 63% of PCs showed robust long-lasting autaptic AR, much stronger than synaptic AR between neighboring PCs. The autaptic AR is mediated predominantly by P/Q-type Ca2+ channels, and its strength depends on the intensity of PC activity and the level of residual Ca2+. Further experiments revealed that autaptic AR enhances spiking activities but reduces the temporal precision of post-burst APs. Together, the results show the occurrence of AR at PC autapses, the delayed and persistent glutamate AR causes self-excitation in individual PCs but may desynchronize the autaptic PC population. Thus, glutamatergic autapses should be essential elements in PFC and contribute to cortical information processing.

Synergistic neural computation is greater downstream of recurrent connectivity in organotypic cortical cultures

ABSTRACTCortical information processing requires synergistic integration of input. Understanding the determinants of synergistic integration–a form of computation–in cortical circuits is therefore a critical step in understanding the functional principles underlying cortical information processing. We established previously that synergistic integration varies directly with the strength of feedforward connectivity. What relationship recurrent and feedback connectivity have with synergistic integration remains unknown. To address this, we analyzed the spiking activity of hundreds of well-isolated neurons in organotypic cultures of mouse somatosensory cortex, recorded using a high-density 512-channel microelectrode array. We asked how empirically observed synergistic integration, quantified through partial information decomposition, varied with local functional network structure. Toward that end, local functional network structure was categorized into motifs with varying recurrent and feedback connectivity. We found that synergistic integration was elevated in motifs with greater recurrent connectivity and was decreased in motifs with greater feedback connectivity. These results indicate that the directionality of local connectivity, beyond feedforward connections, has distinct influences on neural computation. Specifically, more upstream recurrence predicts greater downstream computation, but more feedback predicts lesser computation.

DNA Methylation-Mediated Modulation of Endocytosis as Potential Mechanism for Synaptic Function Regulation in Murine Inhibitory Cortical Interneurons

The balance of excitation and inhibition is essential for cortical information processing, relying on the tight orchestration of the underlying subcellular processes. Dynamic transcriptional control by DNA methylation, catalyzed by DNA methyltransferases (DNMTs), and DNA demethylation, achieved by ten–eleven translocation (TET)-dependent mechanisms, is proposed to regulate synaptic function in the adult brain with implications for learning and memory. However, focus so far is laid on excitatory neurons. Given the crucial role of inhibitory cortical interneurons in cortical information processing and in disease, deciphering the cellular and molecular mechanisms of GABAergic transmission is fundamental. The emerging relevance of DNMT and TET-mediated functions for synaptic regulation irrevocably raises the question for the targeted subcellular processes and mechanisms. In this study, we analyzed the role dynamic DNA methylation has in regulating cortical interneuron function. We found that DNMT1 and TET1/TET3 contrarily modulate clathrin-mediated endocytosis. Moreover, we provide evidence that DNMT1 influences synaptic vesicle replenishment and GABAergic transmission, presumably through the DNA methylation-dependent transcriptional control over endocytosis-related genes. The relevance of our findings is supported by human brain sample analysis, pointing to a potential implication of DNA methylation-dependent endocytosis regulation in the pathophysiology of temporal lobe epilepsy, a disease characterized by disturbed synaptic transmission.

Medial entorhinal cortex activates in a traveling wave

SummaryTraveling waves of cortical activity are hypothesized to organize cortical information processing and support interregional communication. Yet, it remains unknown whether interacting areas exhibit the matched traveling waves necessary to support this hypothesized form of interaction. Here, we show that the strongly-interacting medial entorhinal cortex (MEC) and hippocampus exhibit matched traveling waves. We demonstrate that both the field potential and spiking in the MEC exhibit prominent 6-12 Hz ‘theta’ traveling waves matching those of the hippocampus. The theta phase shifts observed along the MEC were accounted for largely by variation in waveform asymmetry. From this, we hypothesize that that gradients in local physiology underlie both the generation of MEC traveling waves and the functional variations observed previously across the MEC.