Numerous recent experiments in humans and other animals demonstrate impaired temporal coordination of neuronal activity in many psychiatric diseases. A prevalent hypothesis is that temporal coordination in high associational areas of the brain, critical for cognition, is brought about by the multiple hierarchies of rhythms the brain generates. Since most brain rhythms are based on inhibition, the goal of this proposal is to examine the contribution of the variety of interneuron classes to the different oscillations and temporal coordination of principal cell assemblies. Inhibition, both oscillatory and non-oscillator, can flexibly congregate and segregate neuronal populations to support fundamental cortical operations. However, the exact contribution of the different classes of interneurons and their cooperation in these flexible operations are poorly understood. The goal of this proposal is to uncover these mechanisms. Our target is the hippocampus because the mechanisms of several oscillations (theta, gamma, sharp wave ripples) and their contribution to navigation and memory have been extensively studied in this brain region. We will follow two strategies to explore and explain the mechanisms of interneuron-controlled grouping and segregation of principal cells. First, we will quantify the firing rate and phase correlations of the various interneuron types uniquely embeddedness in the various network patterns, using optogenetic identification and large scale recording of the neurons in mice. Second, a closed-loop optogenetic activation and silencing of the identified interneurons will be performed to interfere with native network pattern locally. These combined experiments will therefore identify the causal role of the specific interneuron classes in the organization of cell assemblies supporting spatial navigation and memory. The findings will have important implications for mental disease associated with impaired temporal coordination.
Temporal coordination of neuronal activity within and across brain regions is among the most fundamental neuronal operations and impairment of time management is an underlying mechanism of a variety of mental disorders. Our aim is to explain the role of different interneuron classes in the hippocampus in brain state dependent oscillations and the flexible formation of cell assemblies that support spatial navigation and memory. To achieve this goal we combine optogenetic and large-scale recording methods in behaving mice.
|Khodagholy, Dion; Gelinas, Jennifer N; Thesen, Thomas et al. (2015) NeuroGrid: recording action potentials from the surface of the brain. Nat Neurosci 18:310-5|
|Roux, Lisa; Buzsáki, György (2015) Tasks for inhibitory interneurons in intact brain circuits. Neuropharmacology 88:23-Oct|
|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|
|Sullivan, David; Mizuseki, Kenji; Sorgi, Anthony et al. (2014) Comparison of sleep spindles and theta oscillations in the hippocampus. J Neurosci 34:662-74|
|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|
|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|
|Mizuseki, Kenji; Buzsaki, Gyorgy (2013) Preconfigured, skewed distribution of firing rates in the hippocampus and entorhinal cortex. Cell Rep 4:1010-21|
|Stark, Eran; Eichler, Ronny; Roux, Lisa et al. (2013) Inhibition-induced theta resonance in cortical circuits. Neuron 80:1263-76|
Showing the most recent 10 out of 31 publications