Research in the Section on Critical Brain Dynamics is primarily concerned with functions of the neocortex, which is involved in higher cognitive functions e.g. executive decisions and working memory. Our work focuses on the function of the fast neurotransmitters glutamate and GABA and the neuromodulator dopamine at the network level. These neurotransmitters are involved in a variety of disease states such as schizophrenia and epilepsy. More specifically, our research seeks to answer the following question: ? ? How does the cortex achieve and maintain activity states that allow it to encode and process information? ? ? We address this question at the network level because many of the computational properties of the cortex are predicted to emerge out of the collective action of thousands of neurons and cannot be predicted from the behavior of single neurons alone. We use a variety of experimental and computational techniques to monitor and analyze the dynamics of neuronal networks. We use several in vitro approaches that include acute slices from rats and mouse and some of the most complex neuronal slice co-cultures made to date. Recently, we also expanded into in vivo recordings from the anesthetized rat and started to collaborate with other laboratories on recordings from the anesthetized cat, awake monkey, and human EEG recordings. ? ? Our technical goal is to record network activities from hundreds to thousands of neurons simultaneously and to identify the observed neuronal activity patterns. For example, we culture neuronal networks on microelectrode chips to study the development and regulation of neuronal synchronization over many weeks. Or we implant microelectrode arrays in vivo to collect neuronal activities from up to 100 cortical sites simultaneously. Other techniques, which we use to identify the mechanisms behind certain types of neuronal synchronization, are 2-photon recordings in acute brain slices where neurons have been labeled with fluorescent neuronal activity markers. Alternatively, we record from single neurons in combination with multi-electrode arrays to study the participation of individual cells in the network activity. Taking advantage of these techniques, we are in the unique position to study single neuron electrophysiology, synaptic transmission between neurons, and neuronal populations under in vivo-like conditions in vitro or directly in vivo. ? ? Research during the last year was primarily concerned with establishing several new techniques in the lab that allowed further exploration of neuronal avalanches in the neocortex. ? ? (A) Intracellular monitoring of neuronal avalanches in cortical networks? We recently provided the first demonstration that cortical networks operate in a critical state. At this stable state, the network is maximally excitable without being epileptic. Using multi-electrode arrays in combination with organotypic cultures and acute slices, we demonstrated that propagation of synchronized activity in the critical state takes on the form of neuronal avalanches, which are neither wave-like, nor rhythmic, or random. These neuronal avalanches are described by a power law with slope -3/2 and a branching parameter of 1 at which they retain maximal information as they propagate through the network (Beggs and Plenz, 2003). The neuronal avalanches are highly diverse, yet temporally precise at the millisecond time scale and reoccur over many hours. They thus fulfill many of the requirements of a substrate for memory, and suggest that they play a central role in both information transmission and storage in cortex (Beggs and Plenz, 2004). During the last year, we demonstrated that neuronal avalanches emerge in superficial layers of rat medial prefrontal cortex. The spontaneous recurrence of avalanches follows an inverted-U profile of non-linear dopamine-NMDA interaction. These avalanches thus fulfill the first network level dynamics that follows a similar pharmacological profile as know for cognitive functions e.g. working memory (Stewart and Plenz, 2006). ? ? Since then we have established the current avalanche projects: ? A. In July 2005, we entered into a collaboration with the group of Miguel Nicolelis (M. Nicolelis, M. Lebedev) at Duke University. We have demonstrated that neuronal avalanches describe the awake, desynchronized local EEG activity in awake macaque monkeys. A manuscript with these findings has been submitted (Peterman T, Thiagarajan T, Plenz D). ? B. In January 2004, we started to analyze the occurrence of neuronal avalanches in the developing cortex. We have now found in vivo and in vitro that as soon as superficial cortex layers mature, neuronal avalanches in the form of nested theta/gamma-oscillations occur and are regulated by dopamine. A manuscript, summarizing these findings is about to be submitted (Dharmaraj GE, Plenz D)? C. The homeostatic regulation of neuronal avalanches during cortex development is of great importance to developmental questions of stable synchronization in the absence of epilepsy. In particular, young neurons have been shown to be prone to epilepsy. We developed a new incubator to study neuronal synchronization in single networks on microchips for up to 6 weeks in vitro. We found that neuronal avalanches are maintained homeostatically during development despite large changes in network activity levels. This finding demonstrates that neuronal avalanches are robust intrinsic neuronal dynamics that provides regulatory role during development. A manuscript summarizing these findings has been submitted (C.V. Stewart, D. Plenz).? D. Understanding how single cortical neurons participate in neuronal avalanches is of greatest importance to understand the selective neuronal synchronization during avalanche formation. We have established an electrophysiological setup which allows for the simultaneous recording of neuronal avalanches and intracellular membrane potential of identified neurons. This study is the first demonstration of percolation in neuronal networks and has been presented in abstract form at the last Society for Neuroscience conference (Bellay T, Plenz D). The findings of this study are currently combined with the following study and are prepared for publication.? E. We established 2-photon imaging of identified neuronal groups in acute brain slices using fluorescent activity marker and combined this technique with simultaneous recordings of avalanches using microelectrode chips. The combination of these two very powerful techniques further allowed us to confirm the selective nature of synchronization in neuronal avalanches and the break-down of this selectivity under conditions that mimic epilepsy (Shew, W. , Bellay, T. Plenz, D.). ? ? ? (B) We also have several ongoing projects in which new technologies are combined to improve visualization of network states and imaging of brain functions? ? We have an ongoing collaboration with Dr. Pajevic (CIT/DCB/MSCL/NIH) in which we develop new mathematical tools such as functional network architecture derivations in order to analyze activity in large neuronal networks such as the cortex.? ? We established a collaboration with Prof. W. Singers group at the Max-Planck Institute for Brain Research in Germany in which we study neuronal avalanches in the awake monkey during a working memory task (Dr. M. Munk) and neuronal avalanches in the visual cortex of the anesthetized cat (Dr. D. Nicolic). ? ? We also established a collaboration with Prof. M. Mueller at the University of Leipzig, Germany on neuronal avalanches in the EEG recording from normal subjects during the awake state. ? ? We continue our collaboration with Dr. Peter Bassers group (NICHD/NIH) in which our cell culture models are used to study the flux of water molecules as a function of neuronal activity.
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