@article {47017, title = {Optogenetics: 10 years after ChR2 in neurons-views from the community.}, journal = {Nature Neuroscience}, volume = {18}, year = {2015}, month = {2015 Aug 26}, pages = {1202-12}, issn = {1546-1726}, doi = {10.1038/nn.4106}, author = {Adamantidis, Antoine and Arber, Silvia and Bains, Jaideep S and Bamberg, Ernst and Bonci, Antonello and Buzs{\'a}ki, Gy{\"o}rgy and Cardin, Jessica A and Costa, Rui M and Dan, Yang and Goda, Yukiko and Graybiel, Ann M and H{\"a}usser, Michael and Hegemann, Peter and Huguenard, John R and Insel, Thomas R and Janak, Patricia H and Johnston, Daniel and Josselyn, Sheena A and Koch, Christof and Kreitzer, Anatol C and L{\"u}scher, Christian and Malenka, Robert C and Miesenb{\"o}ck, Gero and Nagel, Georg and Roska, Botond and Schnitzer, Mark J and Shenoy, Krishna V and Soltesz, Ivan and Sternson, Scott M and Tsien, Richard W and Tsien, Roger Y and Turrigiano, Gina G and Tye, Kay M and Wilson, Rachel I} } @article {45186, title = {Large-scale, high-density (up to 512 channels) recording of local circuits in behaving animals.}, journal = {Journal of Neurophysiology}, volume = {111}, year = {2014}, month = {2014 Mar}, pages = {1132-49}, abstract = {

Monitoring representative fractions of neurons from multiple brain circuits in behaving animals is necessary for understanding neuronal computation. Here, we describe a system that allows high-channel-count recordings from a small volume of neuronal tissue using a lightweight signal multiplexing headstage that permits free behavior of small rodents. The system integrates multishank, high-density recording silicon probes, ultraflexible interconnects, and a miniaturized microdrive. These improvements allowed for simultaneous recordings of local field potentials and unit activity from hundreds of sites without confining free movements of the animal. The advantages of large-scale recordings are illustrated by determining the electroanatomic boundaries of layers and regions in the hippocampus and neocortex and constructing a circuit diagram of functional connections among neurons in real anatomic space. These methods will allow the investigation of circuit operations and behavior-dependent interregional interactions for testing hypotheses of neural networks and brain function.

}, issn = {1522-1598}, doi = {10.1152/jn.00785.2013}, author = {Berenyi, Antal and Somogyv{\'a}ri, Zolt{\'a}n and Nagy, Anett J and Roux, Lisa and Long, John D and Fujisawa, Shigeyoshi and Stark, Eran and Leonardo, Anthony and Harris, Timothy D and Buzs{\'a}ki, Gy{\"o}rgy} } @article {6508, title = {Vertebrate versus invertebrate neural circuits.}, journal = {Current Biology}, volume = {23}, year = {2013}, month = {2013 Jun 17}, pages = {R504-6}, issn = {1879-0445}, author = {Katz, Paul and Grillner, Sten and Wilson, Rachel and Borst, Alexander and Greenspan, Ralph and Buzs{\'a}ki, Gy{\"o}rgy and Martin, Kevan and Marder, Eve and Kristan, William and Friedrich, Rainer and Chklovskii, Dmitri Mitya} } @article {6490, title = {Activity dynamics and behavioral correlates of CA3 and CA1 hippocampal pyramidal neurons.}, journal = {Hippocampus}, volume = {22}, year = {2012}, month = {2012 Aug}, pages = {1659-80}, abstract = {

The CA3 and CA1 pyramidal neurons are the major principal cell types of the hippocampus proper. The strongly recurrent collateral system of CA3 cells and the largely parallel-organized CA1 neurons suggest that these regions perform distinct computations. However, a comprehensive comparison between CA1 and CA3 pyramidal cells in terms of firing properties, network dynamics, and behavioral correlations is sparse in the intact animal. We performed large-scale recordings in the dorsal hippocampus of rats to quantify the similarities and differences between CA1 (n \> 3,600) and CA3 (n \> 2,200) pyramidal cells during sleep and exploration in multiple environments. CA1 and CA3 neurons differed significantly in firing rates, spike burst propensity, spike entrainment by the theta rhythm, and other aspects of spiking dynamics in a brain state-dependent manner. A smaller proportion of CA3 than CA1 cells displayed prominent place fields, but place fields of CA3 neurons were more compact, more stable, and carried more spatial information per spike than those of CA1 pyramidal cells. Several other features of the two cell types were specific to the testing environment. CA3 neurons showed less pronounced phase precession and a weaker position versus spike-phase relationship than CA1 cells. Our findings suggest that these distinct activity dynamics of CA1 and CA3 pyramidal cells support their distinct computational roles.

}, keywords = {Action Potentials, Animal, Animals, Behavior, CA1 Region, CA3 Region, Electroencephalography, Hippocampal, Long-Evans, Male, Maze Learning, Nonparametric, Pyramidal Cells, Rats, Statistics, Theta Rhythm}, issn = {1098-1063}, doi = {10.1002/hipo.22002}, author = {Mizuseki, Kenji and Royer, S{\'e}bastien and Diba, Kamran and Buzs{\'a}ki, Gy{\"o}rgy} } @article {5924, title = {Control of timing, rate and bursts of hippocampal place cells by dendritic and somatic inhibition.}, journal = {Nature neuroscience}, volume = {15}, year = {2012}, month = {2012 May}, pages = {769-75}, abstract = {A consortium of inhibitory neurons control the firing patterns of pyramidal cells, but their specific roles in the behaving animal are largely unknown. We performed simultaneous physiological recordings and optogenetic silencing of either perisomatic (parvalbumin (PV) expressing) or dendrite-targeting (somatostatin (SOM) expressing) interneurons in hippocampal area CA1 of head-fixed mice actively moving a treadmill belt rich with visual-tactile stimuli. Silencing of either PV or SOM interneurons increased the firing rates of pyramidal cells selectively in their place fields, with PV and SOM interneurons having their largest effect during the rising and decaying parts of the place field, respectively. SOM interneuron silencing powerfully increased burst firing without altering the theta phase of spikes. In contrast, PV interneuron silencing had no effect on burst firing, but instead shifted the spikes{\textquoteright} theta phase toward the trough of theta. These findings indicate that perisomatic and dendritic inhibition have distinct roles in controlling the rate, burst and timing of hippocampal pyramidal cells.}, keywords = {Action Potentials, Animal, Animals, Behavior, Biophysics, Dendrites, Electric Stimulation, Exercise Test, Green Fluorescent Proteins, Halorhodopsins, Hippocampus, Humans, Inbred C57BL, Light, Mice, Movement, Neural Inhibition, Neurons, Optics and Photonics, Parvalbumins, Patch-Clamp Techniques, Photic Stimulation, Probability, Somatostatin, Spectrum Analysis, Time Factors, Time Perception, Touch, Transgenic}, issn = {1546-1726}, doi = {10.1038/nn.3077}, author = {Royer, S{\'e}bastien and Zemelman, Boris V and Losonczy, Attila and Kim, Jinhyun and Chance, Frances and Magee, Jeffrey C and Buzs{\'a}ki, Gy{\"o}rgy} } @article {6301, title = {A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing.}, journal = {Nature Neuroscience}, volume = {15}, year = {2012}, month = {2012 May}, pages = {793-802}, abstract = {

Cell type-specific expression of optogenetic molecules allows temporally precise manipulation of targeted neuronal activity. Here we present a toolbox of four knock-in mouse lines engineered for strong, Cre-dependent expression of channelrhodopsins ChR2-tdTomato and ChR2-EYFP, halorhodopsin eNpHR3.0 and archaerhodopsin Arch-ER2. All four transgenes mediated Cre-dependent, robust activation or silencing of cortical pyramidal neurons in vitro and in vivo upon light stimulation, with ChR2-EYFP and Arch-ER2 demonstrating light sensitivity approaching that of in utero or virally transduced neurons. We further show specific photoactivation of parvalbumin-positive interneurons in behaving ChR2-EYFP reporter mice. The robust, consistent and inducible nature of our ChR2 mice represents a significant advance over previous lines, and the Arch-ER2 and eNpHR3.0 mice are to our knowledge the first demonstration of successful conditional transgenic optogenetic silencing. When combined with the hundreds of available Cre driver lines, this optimized toolbox of reporter mice will enable widespread investigations of neural circuit function with unprecedented reliability and accuracy.

}, keywords = {Action Potentials, Animals, Archaeal Proteins, Brain, Electroporation, Halorhodopsins, Integrases, Light, Luminescent Proteins, Mice, Neurogenesis, Neurons, Optics and Photonics, Proteins, Rhodopsin, Transgenic, Wakefulness}, issn = {1546-1726}, doi = {10.1038/nn.3078}, author = {Madisen, Linda and Mao, Tianyi and Koch, Henner and Zhuo, Jia-min and Berenyi, Antal and Fujisawa, Shigeyoshi and Hsu, Yun-Wei A and Garcia, Alfredo J and Gu, Xuan and Zanella, Sebastien and Kidney, Jolene and Gu, Hong and Mao, Yimei and Hooks, Bryan M and Boyden, Edward S and Buzs{\'a}ki, Gy{\"o}rgy and Ramirez, Jan Marino and Jones, Allan R and Svoboda, Karel and Han, Xue and Turner, Eric E and Zeng, Hongkui} } @article {2341, title = {Cell assembly sequences arising from spike threshold adaptation keep track of time in the hippocampus.}, journal = {The Journal of Neuroscience: The Official Journal of the Society for Neuroscience}, volume = {31}, year = {2011}, month = {2011 Feb 23}, pages = {2828-34}, abstract = {

Hippocampal neurons can display reliable and long-lasting sequences of transient firing patterns, even in the absence of changing external stimuli. We suggest that time-keeping is an important function of these sequences, and propose a network mechanism for their generation. We show that sequences of neuronal assemblies recorded from rat hippocampal CA1 pyramidal cells can reliably predict elapsed time (15-20 s) during wheel running with a precision of 0.5 s. In addition, we demonstrate the generation of multiple reliable, long-lasting sequences in a recurrent network model. These sequences are generated in the presence of noisy, unstructured inputs to the network, mimicking stationary sensory input. Identical initial conditions generate similar sequences, whereas different initial conditions give rise to distinct sequences. The key ingredients responsible for sequence generation in the model are threshold-adaptation and a Mexican-hat-like pattern of connectivity among pyramidal cells. This pattern may arise from recurrent systems such as the hippocampal CA3 region or the entorhinal cortex. We hypothesize that mechanisms that evolved for spatial navigation also support tracking of elapsed time in behaviorally relevant contexts.

}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.3773-10.2011}, author = {Itskov, Vladimir and Curto, Carina and Pastalkova, Eva and Buzs{\'a}ki, Gy{\"o}rgy} } @article {4294, title = {Distinct representations and theta dynamics in dorsal and ventral hippocampus.}, journal = {The Journal of Neuroscience: The Official Journal of the Society for Neuroscience}, volume = {30}, year = {2010}, month = {2010 Feb 3}, pages = {1777-87}, abstract = {

Although anatomical, lesion, and imaging studies of the hippocampus indicate qualitatively different information processing along its septo-temporal axis, physiological mechanisms supporting such distinction are missing. We found fundamental differences between the dorsal (dCA3) and the ventral-most parts (vCA3) of the hippocampus in both environmental representation and temporal dynamics. Discrete place fields of dCA3 neurons evenly covered all parts of the testing environments. In contrast, vCA3 neurons (1) rarely showed continuous two-dimensional place fields, (2) differentiated open and closed arms of a radial maze, and (3) discharged similar firing patterns with respect to the goals, both on multiple arms of a radial maze and during opposite journeys in a zigzag maze. In addition, theta power and the fraction of theta-rhythmic neurons were substantially reduced in the ventral compared with dorsal hippocampus. We hypothesize that the spatial representation in the septo-temporal axis of the hippocampus is progressively decreased. This change is paralleled with a reduction of theta rhythm and an increased representation of nonspatial information.

}, keywords = {Animals, Hippocampus, Long-Evans, Male, Maze Learning, Neurons, Rats, Space Perception, Theta Rhythm}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.4681-09.2010}, author = {Royer, S{\'e}bastien and Sirota, Anton and Patel, Jagdish and Buzs{\'a}ki, Gy{\"o}rgy} } @article {2121, title = {Multi-array silicon probes with integrated optical fibers: light-assisted perturbation and recording of local neural circuits in the behaving animal.}, journal = {The European Journal of Neuroscience}, volume = {31}, year = {2010}, month = {2010 Jun}, pages = {2279-91}, abstract = {

Recordings of large neuronal ensembles and neural stimulation of high spatial and temporal precision are important requisites for studying the real-time dynamics of neural networks. Multiple-shank silicon probes enable large-scale monitoring of individual neurons. Optical stimulation of genetically targeted neurons expressing light-sensitive channels or other fast (milliseconds) actuators offers the means for controlled perturbation of local circuits. Here we describe a method to equip the shanks of silicon probes with micron-scale light guides for allowing the simultaneous use of the two approaches. We then show illustrative examples of how these compact hybrid electrodes can be used in probing local circuits in behaving rats and mice. A key advantage of these devices is the enhanced spatial precision of stimulation that is achieved by delivering light close to the recording sites of the probe. When paired with the expression of light-sensitive actuators within genetically specified neuronal populations, these devices allow the relatively straightforward and interpretable manipulation of network activity.

}, keywords = {Action Potentials, Animal, Animals, Behavior, Electric Stimulation, Electrophysiology, Light, Mice, Neurons, Neuropsychological Tests, Optical Fibers, Photic Stimulation, Rats, Recombinant Fusion Proteins, Silicon}, issn = {1460-9568}, doi = {10.1002/cbic.201000254}, author = {Royer, S{\'e}bastien and Zemelman, Boris V and Barbic, Mladen and Losonczy, Attila and Buzs{\'a}ki, Gy{\"o}rgy and Magee, Jeffrey C} } @article {2342, title = {Temporal delays among place cells determine the frequency of population theta oscillations in the hippocampus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {107}, year = {2010}, month = {2010 Apr 27}, pages = {7957-62}, abstract = {

Driven either by external landmarks or by internal dynamics, hippocampal neurons form sequences of cell assemblies. The coordinated firing of these active cells is organized by the prominent "theta" oscillations in the local field potential (LFP): place cells discharge at progressively earlier theta phases as the rat crosses the respective place field ("phase precession"). The faster oscillation frequency of active neurons and the slower theta LFP, underlying phase precession, creates a paradox. How can faster oscillating neurons comprise a slower population oscillation, as reflected by the LFP? We built a mathematical model that allowed us to calculate the population activity analytically from experimentally derived parameters of the single neuron oscillation frequency, firing field size (duration), and the relationship between within-theta delays of place cell pairs and their distance representations ("compression"). The appropriate combination of these parameters generated a constant frequency population rhythm along the septo-temporal axis of the hippocampus, while allowing individual neurons to vary their oscillation frequency and field size. Our results suggest that the faster-than-theta oscillations of pyramidal cells are inherent and that phase precession is a result of the coordinated activity of temporally shifted cell assemblies, relative to the population activity, reflected by the LFP.

}, keywords = {Action Potentials, Animals, Hippocampus, Locomotion, Models, Neurological, Pyramidal Cells, Rats, Theta Rhythm}, issn = {1091-6490}, doi = {10.1523/JNEUROSCI.3773-10.2011}, author = {Geisler, Caroline and Diba, Kamran and Pastalkova, Eva and Mizuseki, Kenji and Royer, S{\'e}bastien and Buzs{\'a}ki, Gy{\"o}rgy} } @article {2343, title = {Theta oscillations provide temporal windows for local circuit computation in the entorhinal-hippocampal loop.}, journal = {Neuron}, volume = {64}, year = {2009}, month = {2009 Oct 29}, pages = {267-80}, abstract = {

Theta oscillations are believed to play an important role in the coordination of neuronal firing in the entorhinal (EC)-hippocampal system but the underlying mechanisms are not known. We simultaneously recorded from neurons in multiple regions of the EC-hippocampal loop and examined their temporal relationships. Theta-coordinated synchronous spiking of EC neuronal populations predicted the timing of current sinks in target layers in the hippocampus. However, the temporal delays between population activities in successive anatomical stages were longer (typically by a half theta cycle) than expected from axon conduction velocities and passive synaptic integration of feed-forward excitatory inputs. We hypothesize that the temporal windows set by the theta cycles allow for local circuit interactions and thus a considerable degree of computational independence in subdivisions of the EC-hippocampal loop.

}, keywords = {Action Potentials, Animals, Electric Stimulation, Entorhinal Cortex, Hippocampus, Long-Evans, Long-Term Potentiation, Male, Models, Movement, Nerve Net, Neural Inhibition, Neural Pathways, Neurological, Neurons, Patch-Clamp Techniques, Rats, Reaction Time, Synaptic Transmission, Theta Rhythm}, issn = {1097-4199}, doi = {10.1523/JNEUROSCI.3773-10.2011}, author = {Mizuseki, Kenji and Sirota, Anton and Pastalkova, Eva and Buzs{\'a}ki, Gy{\"o}rgy} } @article {2345, title = {Internally generated cell assembly sequences in the rat hippocampus.}, journal = {Science}, volume = {321}, year = {2008}, month = {2008 Sep 5}, pages = {1322-7}, abstract = {

A long-standing conjecture in neuroscience is that aspects of cognition depend on the brain{\textquoteright}s ability to self-generate sequential neuronal activity. We found that reliably and continually changing cell assemblies in the rat hippocampus appeared not only during spatial navigation but also in the absence of changing environmental or body-derived inputs. During the delay period of a memory task, each moment in time was characterized by the activity of a particular assembly of neurons. Identical initial conditions triggered a similar assembly sequence, whereas different conditions gave rise to different sequences, thereby predicting behavioral choices, including errors. Such sequences were not formed in control (nonmemory) tasks. We hypothesize that neuronal representations, evolved for encoding distance in spatial navigation, also support episodic recall and the planning of action sequences.

}, keywords = {Action Potentials, Animal, Animals, Behavior, Choice Behavior, Cues, Hippocampus, Interneurons, Long-Evans, Male, Maze Learning, Memory, Mental Recall, Models, Motor Activity, Neurological, Pyramidal Cells, Rats}, issn = {1095-9203}, doi = {10.1523/JNEUROSCI.3773-10.2011}, author = {Pastalkova, Eva and Itskov, Vladimir and Amarasingham, Asohan and Buzs{\'a}ki, Gy{\"o}rgy} } @article {2346, title = {Theta-mediated dynamics of spatial information in hippocampus.}, journal = {The Journal of Neuroscience: The Official Journal of the Society for Neuroscience}, volume = {28}, year = {2008}, month = {2008 Jun 4}, pages = {5959-64}, abstract = {

In rodent hippocampus, neuronal activity is organized by a 6-10 Hz theta oscillation. The spike timing of hippocampal pyramidal cells with respect to the theta rhythm correlates with an animal{\textquoteright}s position in space. This correlation has been suggested to indicate an explicit temporal code for position. Alternatively, it may be interpreted as a byproduct of theta-dependent dynamics of spatial information flow in hippocampus. Here we show that place cell activity on different phases of theta reflects positions shifted into the future or past along the animal{\textquoteright}s trajectory in a two-dimensional environment. The phases encoding future and past positions are consistent across recorded CA1 place cells, indicating a coherent representation at the network level. Consistent theta-dependent time offsets are not simply a consequence of phase-position correlation (phase precession), because they are no longer seen after data randomization that preserves the phase-position relationship. The scale of these time offsets, 100-300 ms, is similar to the latencies of hippocampal activity after sensory input and before motor output, suggesting that offset activity may maintain coherent brain activity in the face of information processing delays.

}, keywords = {Action Potentials, Animals, Hippocampus, Long-Evans, Male, Rats, Spatial Behavior, Theta Rhythm}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.3773-10.2011}, author = {Itskov, Vladimir and Pastalkova, Eva and Mizuseki, Kenji and Buzs{\'a}ki, Gy{\"o}rgy and Harris, Kenneth D} }