Neuroscientists monitor extracellular brain signals to infer the underlying neural mechanisms of computation and cognition. While intracellular and transmembrane processes have monopolized the interest of researchers, much less attention has been paid to extracellular eld eects. Yet, the quality and quantity of information retrieved from extracellular recording sessions critically depends on our understanding of the transfer function between intracellular activity and the ex- tracellular space. Moreover, it has been shown that endogenous extracellular elds do aect the state and function of individual neurons through ephaptic coupling. This provides a continuous non-synaptic feedback mechanism between the eld and individual neurons. In a collaborative eort, the laboratories of C. Koch and G. Buzsaki propose to unravel the origin and functionality of extracellular eld eects in the hippocampal CA1 region during theta and sharp waves activity by using a modeling/experimental approach. Computationally, by modeling a large number of biophysical realistic pyramidal and inhibitory interneurons making up the rat CA1 hippocampus subeld. These, in conjunction with glia cells, will be arranged in a 3-D resistive cytoplasm, and their extracellular contributions will be summed to yield the nal extracellular electrical potential associated with electrical activity in individual neurons. Patch-clamp experiments from individ- ual hippocampal neurons will shed light onto the intracellular and extracellular correlates of CA1 pattern activity. Recordings from anesthetized rats will be used to constrain these models and to test their accuracy. Simultaneous optical stimulation (in CA3 using ChR2 and related optogenetic techniques) and extracellular recording experiments in CA1 will be performed to manipulate ex- tracellular brain activity to answer a series of questions: (i) what is the detailed makeup of the extracellular eld in the hippocampus, (ii) what are its contributors (pre- versus post-synaptic ac- tivity, spiking currents, glia), and (iii) how does the eld serve to synchronize the underlying sub- and suprathreshold activity of CA1 neurons - even in the absence of direct synaptic coupling. This research will also bear on our understanding of a number of pathologies and their treatment, in particular on the initiation and spread of pathological hypersynchronziation, such as in epilepsy, and the short- and long-range eect of direct brain stimulation via electrical current, as in deep brain stimulation. Here, therapy ecacy crucially depends on a solid understanding of the eect of extracellular elds on neurons and neural circuits.
The aim of this project is to analyze the origin of the electric eld measured inside the brain and how changes in this eld aect brain processes. This electrical eld is most likely important in propagating hyper-synchronous electrical discharges during epileptic seizures. Deep brain stimula- tion, as frequently used to treat Parkinsons disease and some forms of depression, will also directly aect this electrical eld with ill-understood consequences. It is thus essential to study the direct and indirect biophysical eects of electrical elds, either endogenous or imposed.
|Roux, Lisa; Stark, Eran; Sjulson, Lucas et al. (2014) In vivo optogenetic identification and manipulation of GABAergic interneuron subtypes. Curr Opin Neurobiol 26:88-95|
|Schomburg, Erik W; Fernández-Ruiz, Antonio; Mizuseki, Kenji et al. (2014) Theta phase segregation of input-specific gamma patterns in entorhinal-hippocampal networks. Neuron 84:470-85|
|Stark, Eran; Roux, Lisa; Eichler, Ronny et al. (2014) Pyramidal cell-interneuron interactions underlie hippocampal ripple oscillations. Neuron 83:467-80|
|Berenyi, Antal; Somogyvari, Zoltan; Nagy, Anett J et al. (2014) Large-scale, high-density (up to 512 channels) recording of local circuits in behaving animals. J Neurophysiol 111:1132-49|
|Vandecasteele, Marie; Varga, Viktor; Berényi, Antal et al. (2014) Optogenetic activation of septal cholinergic neurons suppresses sharp wave ripples and enhances theta oscillations in the hippocampus. Proc Natl Acad Sci U S A 111:13535-40|
|Diba, Kamran; Amarasingham, Asohan; Mizuseki, Kenji et al. (2014) Millisecond timescale synchrony among hippocampal neurons. J Neurosci 34:14984-94|
|Agarwal, Gautam; Stevenson, Ian H; Berényi, Antal et al. (2014) Spatially distributed local fields in the hippocampus encode rat position. Science 344:626-30|
|Buzsáki, György; Mizuseki, Kenji (2014) The log-dynamic brain: how skewed distributions affect network operations. Nat Rev Neurosci 15:264-78|
|Mizuseki, Kenji; Buzsaki, Gyorgy (2014) Theta oscillations decrease spike synchrony in the hippocampus and entorhinal cortex. Philos Trans R Soc Lond B Biol Sci 369:20120530|
|Patel, Jagdish; Schomburg, Erik W; Berenyi, Antal et al. (2013) Local generation and propagation of ripples along the septotemporal axis of the hippocampus. J Neurosci 33:17029-41|
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