Neuronal Avalanches in the Neocortex

National Institute Of Mental Health

Investigators

Linked publications & trials

Abstract

1. We demonstrated for the first time that the temporal profile of neuronal avalanches in space exhibits is an inverted parabola equating a critical shape exponent of 2. This finding obtained with cellular resolution in transgenic mouse in vivo during quiet resting and visual procession with and without locomotion in primary as well as frontal cortices. The findings obtained with advanced 2-photon imaging technology demonstrate a robust, general biomarker for avalanche dynamics in the normal brain. More precisely, we addressed and solved the following main problem(s): Neurons in the cerebral cortex fire coincident action potentials during ongoing activity and in response to sensory inputs. These synchronized cell assemblies are fundamental to cortex function, yet basic dynamical aspects of their size and duration are largely unknown. Using 2-photon imaging of neurons in the superficial cortex of awake mice, we show that synchronized cell assemblies organize as scale-invariant avalanches that quadratically grow with duration. The quadratic avalanche scaling was only found for correlated neurons, required temporal coarse-graining to compensate for spatial subsampling of the imaged cortex, and suggested cortical dynamics to be critical as demonstrated in simulations of balanced Excitation/Inhibition-networks. The corresponding time course of an inverted parabola with exponent of = 2 described cortical avalanches of coincident firing for up to 5s duration and over an areaof 1 mm2. These parabolic avalanches maximized temporal complexity in the ongoing activity of prefrontal and somatosensory cortex and in visual responses of primary visual cortex. Our results identify a scale-invariant temporal order in the synchronization of highly diverse cortical cell assemblies in the form of parabolic avalanches. Capek, Ribeiro et al., 2023 Nature Communication. 2. We demonstrated that our previous identification of the Omori-Utsu law for neuronal avalanches in mature cell cultures and nonhuman primates is embedded in the waxing-waning alpha-rhythm of the human brain during wakefulness. This statistical fingerprint of neuronal avalanches during wakefulness is absent during sleep states. This finding, identified in humans using non-invasive fMRI as well as ECoG suggests a new robust biomarker for wakefulness in human or general, mammalian brains. More precisely, we addressed and solved the following main problem(s): The alpha rhythm is a distinctive feature of the awake resting-state of the human brain. Recent evidence suggests that alpha plays an active role in information processing, modulating behavioral and cognitive performance. However, the relationship between alpha oscillations and the underlying neuronal dynamics remains poorly understood. To address this question, we investigate collective neural activity during resting wake and NREM sleep, a physiologic state with marginal presence of alpha rhythm. We show that, during resting wake, alpha oscillations drive alternation of attenuation and amplification bouts in neural activity. Our analysis indicates that inhibition is activated in pulses that last a single alpha cycle and gradually suppress neural activity, while excitation is successively enhanced over the timescales of a few alpha cycles to amplify neural activity. Furthermore, we show that long-term, intermittent fluctuations in alpha amplitudeknown as the waxing and waning phenomenonare associated with an attenuation-amplification mechanism acting over the timescales of several seconds and described by a power law decay of the activity rate in the waning phase. Importantly, we do not observe such dynamics during NREM sleep. The results suggest that the alpha rhythm functions as a pacemaker for the alternation of inhibition and excitation bouts across multiple timescales, the waxing and waning being a long-term control mechanism of cortical excitability. The amplification regime observed beyond the timescales of the individual alpha cycle suggests in turn that alpha oscillations might modulate the intensity of neural activity not only through pulses of inhibition, as proposed in the pulsed inhibition hypothesis, but also by timely enhancing excitation (or dis-inhibition). Lombardi et al., 2023 Cell Reports 3. We introduced in collaboration with 2 NICHD laboratories a robust, yet highly efficient model on oligodendrocyte function in the brain. The model suggest how oligodendrocytes can maintain and event strengthen synchronized fiber volley activity along long-white matter fiber bundles in large brains. The model provides a solution how long-range synchronization during neuronal avalanches can be robustly obtained in large mammalian brains and thus gives credence to theory on brain functions that rely on select neuronal synchronization. More precisely, we addressed and solved the following main problem(s): Temporal synchrony of signals arriving from different neurons or brain regions is essential for proper neural processing. Nevertheless, it is not well understood how such synchrony is achieved and maintained in a complex network of time-delayed neural interactions. Myelin plasticity, accomplished by oligodendrocytes (OLs), has been suggested as an efficient mechanism for controlling timing in brain communications through adaptive changes of axonal conduction velocity and consequently conduction time delays, or latencies; however, local rules and feedback mechanisms that OLs use to achieve synchronization are not known. We propose a mathematical model of oligodendrocyte-mediated myelin plasticity (OMP) in which OLs play an active role in providing such feedback. This is achieved without using arrival times at the synapse or modulatory signaling from astrocytes; instead, it relies on the presence of global and transient OL responses to local action potentials in the axons they myelinate. While inspired by OL morphology, we provide the theoretical underpinnings that motivated the model and explore its performance for a wide range of its parameters. Our results indicate that when the characteristic time of OLs transient intracellular responses to neural spikes is between 10 and 40 ms and the firing rates in individual axons are relatively low (10 Hz), the OMP model efficiently synchronizes correlated and time-locked signals while latencies in axons carrying independent signals are unaffected. This suggests a novel form of selective synchronization in the CNS in which oligodendrocytes play an active role by modulating the conduction delays of correlated spike trains as they traverse to their targets. Pajevic et al., 2023.