We previously described neuronal avalanches as a fundamental synchronization dynamics of the cortex. The neuronal avalanches were found to have several unique properties: ? ? 1. In the adult brain, neuronal avalanches are localized to the upper cortical layers, exactly those layers that are considered crucial for many higher cortical functions. ? ? 2. The regulation and dysregulation of neuronal avalanches exhibits a very similar pharmacological profile to the regulation and dysregulation of working memory function in humans and schizophrenic patients. ? ? Because many mental illnesses have a strong developmental component responsible for dysfunctions in the adult brain, we focused this year on the role of neuronal avalanches during development. Specifically, we wanted to know ? ? a. When and where do neuronal avalanches emerge in the developing cortex?? b. How are neuronal avalanches regulated during development?? c. Are neuronal avalanches homeostatically regulated?? ? The development of the cortex is marked by distinct patterns of synchronized neuronal activity that emerge spontaneously, are preserved across different species, regulate neuronal differentiation and synapse formation, and serve as a substrate for information processing. Knowledge of the precise nature of these patterns significantly contributes to our understanding of normal and abnormal brain development. ? ? Activity patterns in superficial layers due to their complex and variable nature are only poorly understood. Using microelectrode array recordings in vivo and in vitro, we for the first time demonstrate (Gireesh and Plenz, 2008) that the development of superficial layers in cortex is marked by the emergence of nested theta- and beta/gamma-oscillations, which require NMDA and GABAAmediated synaptic transmission. The oscillations organize as neuronal avalanches, i.e. they are synchronized across cortical sites forming diverse and millisecond-precise spatiotemporal patterns that distribute in sizes according to a power law with a slope of -1.5. Importantly, the correspondence between nested oscillations and neuronal avalanches requires activation of the dopamine D1receptor.? ? The linking of the synchronization during fast beta/gamma-oscillations with an absolute criterion, i.e. the power law exponent of -1.5 for neuronal avalanches, might allow for a simple and direct evaluation of the amount of oscillation synchrony for the default network state of cortical layer 2/3. Conversely, a deviation from -1.5 could identify pathological conditions related to cortical oscillations, NMDA-receptor functioning, and dopamine during development, as e.g. suggested for schizophrenia.? ? Our findings unify two seemingly different views of neuronal synchronization oscillations and avalanches and suggest that the repetitive formation of neuronal avalanches provides an intrinsic and optimal template for the selective linking of external inputs to developing superficial layers. ? ? ? In a second project, we expanded our methodology to study neuronal avalanches in stable and robust in vitro assays. Of high importance is the homeostatic regulation of neuronal avalanches during cortex development given that young cortical neurons are particularly prone to epilepsy. We developed new incubator technology as well as new algorithms to study neuronal avalanches in single cortex cultures on microchips for up to 6 weeks in vitro. We found that neuronal avalanches are maintained homeostatically during development despite large changes in neuronal activity levels of the network.? ? This finding demonstrates for the first time that neuronal avalanches are a robust intrinsic neuronal dynamics of superficial layers that is maintained throughout cortex development (C.V. Stewart and D. Plenz, 2007).
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