TY - JOUR AU - Gridchyn, Igor AU - Schönenberger, Philipp AU - O'Neill, Joseph AU - Csicsvari, Jozsef L ID - 7684 IS - 2 JF - Neuron SN - 08966273 TI - Assembly-specific disruption of hippocampal replay leads to selective memory deficit VL - 106 ER - TY - JOUR AB - In vitro work revealed that excitatory synaptic inputs to hippocampal inhibitory interneurons could undergo Hebbian, associative, or non-associative plasticity. Both behavioral and learning-dependent reorganization of these connections has also been demonstrated by measuring spike transmission probabilities in pyramidal cell-interneuron spike cross-correlations that indicate monosynaptic connections. Here we investigated the activity-dependent modification of these connections during exploratory behavior in rats by optogenetically inhibiting pyramidal cell and interneuron subpopulations. Light application and associated firing alteration of pyramidal and interneuron populations led to lasting changes in pyramidal-interneuron connection weights as indicated by spike transmission changes. Spike transmission alterations were predicted by the light-mediated changes in the number of pre- and postsynaptic spike pairing events and by firing rate changes of interneurons but not pyramidal cells. This work demonstrates the presence of activity-dependent associative and non-associative reorganization of pyramidal-interneuron connections triggered by the optogenetic modification of the firing rate and spike synchrony of cells. AU - Gridchyn, Igor AU - Schönenberger, Philipp AU - O'Neill, Joseph AU - Csicsvari, Jozsef L ID - 8740 JF - eLife TI - Optogenetic inhibition-mediated activity-dependent modification of CA1 pyramidal-interneuron connections during behavior VL - 9 ER - TY - JOUR AB - Hippocampal activity patterns representing movement trajectories are reactivated in immobility and sleep periods, a process associated with memory recall, consolidation, and decision making. It is thought that only fixed, behaviorally relevant patterns can be reactivated, which are stored across hippocampal synaptic connections. To test whether some generalized rules govern reactivation, we examined trajectory reactivation following non-stereotypical exploration of familiar open-field environments. We found that random trajectories of varying lengths and timescales were reactivated, resembling that of Brownian motion of particles. The animals’ behavioral trajectory did not follow Brownian diffusion demonstrating that the exact behavioral experience is not reactivated. Therefore, hippocampal circuits are able to generate random trajectories of any recently active map by following diffusion dynamics. This ability of hippocampal circuits to generate representations of all behavioral outcome combinations, experienced or not, may underlie a wide variety of hippocampal-dependent cognitive functions such as learning, generalization, and planning. AU - Stella, Federico AU - Baracskay, Peter AU - O'Neill, Joseph AU - Csicsvari, Jozsef L ID - 6338 JF - Neuron TI - Hippocampal reactivation of random trajectories resembling Brownian diffusion VL - 102 ER - TY - JOUR AB - Hippocampus is needed for both spatial working and reference memories. Here, using a radial eight-arm maze, we examined how the combined demand on these memories influenced CA1 place cell assemblies while reference memories were partially updated. This was contrasted with control tasks requiring only working memory or the update of reference memory. Reference memory update led to the reward-directed place field shifts at newly rewarded arms and to the gradual strengthening of firing in passes between newly rewarded arms but not between those passes that included a familiar-rewarded arm. At the maze center, transient network synchronization periods preferentially replayed trajectories of the next chosen arm in reference memory tasks but the previously visited arm in the working memory task. Hence, reference memory demand was uniquely associated with a gradual, goal novelty-related reorganization of place cell assemblies and with trajectory replay that reflected the animal's decision of which arm to visit next. AU - Xu, Haibing AU - Baracskay, Peter AU - O'Neill, Joseph AU - Csicsvari, Jozsef L ID - 5828 IS - 1 JF - Neuron SN - 10974199 TI - Assembly responses of hippocampal CA1 place cells predict learned behavior in goal-directed spatial tasks on the radial eight-arm maze VL - 101 ER - TY - JOUR AB - Grid cells with their rigid hexagonal firing fields are thought to provide an invariant metric to the hippocampal cognitive map, yet environmental geometrical features have recently been shown to distort the grid structure. Given that the hippocampal role goes beyond space, we tested the influence of nonspatial information on the grid organization. We trained rats to daily learn three new reward locations on a cheeseboard maze while recording from the medial entorhinal cortex and the hippocampal CA1 region. Many grid fields moved toward goal location, leading to long-lasting deformations of the entorhinal map. Therefore, distortions in the grid structure contribute to goal representation during both learning and recall, which demonstrates that grid cells participate in mnemonic coding and do not merely provide a simple metric of space. AU - Boccara, Charlotte N. AU - Nardin, Michele AU - Stella, Federico AU - O'Neill, Joseph AU - Csicsvari, Jozsef L ID - 6194 IS - 6434 JF - Science SN - 0036-8075 TI - The entorhinal cognitive map is attracted to goals VL - 363 ER - TY - JOUR AB - The hippocampus is thought to initiate systems-wide mnemonic processes through the reactivation of previously acquired spatial and episodic memory traces, which can recruit the entorhinal cortex as a first stage of memory redistribution to other brain areas. Hippocampal reactivation occurs during sharp wave-ripples, in which synchronous network firing encodes sequences of places.We investigated the coordination of this replay by recording assembly activity simultaneously in the CA1 region of the hippocampus and superficial layers of the medial entorhinal cortex. We found that entorhinal cell assemblies can replay trajectories independently of the hippocampus and sharp wave-ripples. This suggests that the hippocampus is not the sole initiator of spatial and episodic memory trace reactivation. Memory systems involved in these processes may include nonhierarchical, parallel components. AU - O'Neill, Joseph AU - Boccara, Charlotte AU - Stella, Federico AU - Schönenberger, Philipp AU - Csicsvari, Jozsef L ID - 1132 IS - 6321 JF - Science SN - 00368075 TI - Superficial layers of the medial entorhinal cortex replay independently of the hippocampus VL - 355 ER - TY - JOUR AB - During hippocampal sharp wave/ripple (SWR) events, previously occurring, sensory inputdriven neuronal firing patterns are replayed. Such replay is thought to be important for plasticity- related processes and consolidation of memory traces. It has previously been shown that the electrical stimulation-induced disruption of SWR events interferes with learning in rodents in different experimental paradigms. On the other hand, the cognitive map theory posits that the plastic changes of the firing of hippocampal place cells constitute the electrophysiological counterpart of the spatial learning, observable at the behavioral level. Therefore, we tested whether intact SWR events occurring during the sleep/rest session after the first exploration of a novel environment are needed for the stabilization of the CA1 code, which process requires plasticity. We found that the newly-formed representation in the CA1 has the same level of stability with optogenetic SWR blockade as with a control manipulation that delivered the same amount of light into the brain. Therefore our results suggest that at least in the case of passive exploratory behavior, SWR-related plasticity is dispensable for the stability of CA1 ensembles. AU - Kovács, Krisztián AU - O'Neill, Joseph AU - Schönenberger, Philipp AU - Penttonen, Markku AU - Rangel Guerrero, Dámaris K AU - Csicsvari, Jozsef L ID - 1279 IS - 10 JF - PLoS One TI - Optogenetically blocking sharp wave ripple events in sleep does not interfere with the formation of stable spatial representation in the CA1 area of the hippocampus VL - 11 ER - TY - JOUR AB - Hippocampal neurons encode a cognitive map of space. These maps are thought to be updated during learning and in response to changes in the environment through activity-dependent synaptic plasticity. Here we examine how changes in activity influence spatial coding in rats using halorhodopsin-mediated, spatially selective optogenetic silencing. Halorhoposin stimulation leads to light-induced suppression in many place cells and interneurons; some place cells increase their firing through disinhibition, whereas some show no effect. We find that place fields of the unaffected subpopulation remain stable. On the other hand, place fields of suppressed place cells were unstable, showing remapping across sessions before and after optogenetic inhibition. Disinhibited place cells had stable maps but sustained an elevated firing rate. These findings suggest that place representation in the hippocampus is constantly governed by activity-dependent processes, and that disinhibition may provide a mechanism for rate remapping. AU - Schönenberger, Philipp AU - O'Neill, Joseph AU - Csicsvari, Jozsef L ID - 1334 JF - Nature Communications TI - Activity dependent plasticity of hippocampal place maps VL - 7 ER - TY - JOUR AB - Learning can be facilitated by previous knowledge when it is organized into relational representations forming schemas. In this issue of Neuron, McKenzie et al. (2014) demonstrate that the hippocampus rapidly forms interrelated, hierarchical memory representations to support schema-based learning. AU - O'Neill, Joseph AU - Csicsvari, Jozsef L ID - 2003 IS - 1 JF - Neuron TI - Learning by example in the hippocampus VL - 83 ER - TY - JOUR AB - In the hippocampus, cell assemblies forming mnemonic representations of space are thought to arise as a result of changes in functional connections of pyramidal cells. We have found that CA1 interneuron circuits are also reconfigured during goal-oriented spatial learning through modification of inputs from pyramidal cells. As learning progressed, new pyramidal assemblies expressed in theta cycles alternated with previously established ones, and eventually overtook them. The firing patterns of interneurons developed a relationship to new, learning-related assemblies: some interneurons associated their activity with new pyramidal assemblies while some others dissociated from them. These firing associations were explained by changes in the weight of monosynaptic inputs received by interneurons from new pyramidal assemblies, as these predicted the associational changes. Spatial learning thus engages circuit modifications in the hippocampus that incorporate a redistribution of inhibitory activity that might assist in the segregation of competing pyramidal cell assembly patterns in space and time. AU - Dupret, David AU - O'Neill, Joseph AU - Csicsvari, Jozsef L ID - 2860 IS - 1 JF - Neuron TI - Dynamic reconfiguration of hippocampal interneuron circuits during spatial learning VL - 78 ER - TY - JOUR AB - The hippocampus is an important brain circuit for spatial memory and the spatially selective spiking of hippocampal neuronal assemblies is thought to provide a mnemonic representation of space. We found that remembering newly learnt goal locations required NMDA receptorĝ€"dependent stabilization and enhanced reactivation of goal-related hippocampal assemblies. During spatial learning, place-related firing patterns in the CA1, but not CA3, region of the rat hippocampus were reorganized to represent new goal locations. Such reorganization did not occur when goals were marked by visual cues. The stabilization and successful retrieval of these newly acquired CA1 representations of behaviorally relevant places was NMDAR dependent and necessary for subsequent memory retention performance. Goal-related assembly patterns associated with sharp wave/ripple network oscillations, during both learning and subsequent rest periods, predicted memory performance. Together, these results suggest that the reorganization and reactivation of assembly firing patterns in the hippocampus represent the formation and expression of new spatial memory traces. © 2010 Nature America, Inc. All rights reserved. AU - Dupret, David AU - Joseph O'Neill AU - Pleydell-Bouverie, Barty AU - Jozsef Csicsvari ID - 3441 IS - 8 JF - Nature Neuroscience TI - The reorganization and reactivation of hippocampal maps predict spatial memory performance VL - 13 ER - TY - JOUR AB - Episodic and spatial memories each involve the encoding of complex associations in hippocampal neuronal circuits. Such memory traces could be stabilised from short- to long-term forms by consolidation processes involving the 'reactivation' of the original network firing patterns during sleep and rest. Waking experience can be replayed in many different brain areas, but an important role for the hippocampus lies in the organisation of the 'reactivation' process. Emerging evidence suggests that sharp wave/ripple (SWR) events in the hippocampus could coordinate the reactivation of memory traces and direct their reinstatement in cortical circuits. Although the mechanisms remain uncertain, there is a growing consensus that such SWR-directed reactivation of brain-wide memory traces could underlie memory consolidation. © 2010 Elsevier Ltd. AU - Joseph O'Neill AU - Pleydell-Bouverie, Barty AU - Dupret, David AU - Jozsef Csicsvari ID - 3442 IS - 5 JF - Trends in Neurosciences TI - Play it again: reactivation of waking experience and memory VL - 33 ER - TY - JOUR AB - The hippocampus is thought to be involved in episodic memory formation by reactivating traces of waking experience during sleep. Indeed, the joint firing of spatially tuned pyramidal cells encoding nearby places recur during sleep. We found that the sleep cofiring of rat CA1 pyramidal cells encoding similar places increased relative to the sleep session before exploration. This cofiring increase depended on the number of times that cells fired together with short latencies ( < 50 ms) during exploration, and was strongest between cells representing the most visited places. This is indicative of a Hebbian learning rule in which changes in firing associations between cells are determined by the number of waking coincident firing events. In contrast, cells encoding different locations reduced their cofiring in proportion to the number of times that they fired independently. Together these data indicate that reactivated patterns are shaped by both positive and negative changes in cofiring, which are determined by recent behavior. AU - Joseph O'Neill AU - Senior,Timothy J AU - Allen, Kevin AU - Huxter,John R AU - Jozsef Csicsvari ID - 3520 IS - 2 JF - Nature Neuroscience TI - Reactivation of experience-dependent cell assembly patterns in the hippocampus VL - 11 ER - TY - JOUR AB - Hippocampal place cells that fire together within the same cycle of theta oscillations represent the sequence of positions (movement trajectory) that a rat traverses on a linear track. Furthermore, it has been suggested that the encoding of these and other types of temporal memory sequences is organized by gamma oscillations nested within theta oscillations. Here, we examined whether gamma-related firing of place cells permits such discrete temporal coding. We found that gamma-modulated CA1 pyramidal cells separated into two classes on the basis of gamma firing phases during waking theta periods. These groups also differed in terms of their spike waveforms, firing rates, and burst firing tendency. During gamma oscillations one group's firing became restricted to theta phases associated with the highest gamma power. Consequently, on the linear track, cells in this group often failed to fire early in theta-phase precession (as the rat entered the place field) if gamma oscillations were present. The second group fired throughout the theta cycle during gamma oscillations, and maintained gamma-modulated firing at different stages of theta-phase precession. Our results suggest that the two different pyramidal cell classes may support different types of population codes within a theta cycle: one in which spike sequences representing movement trajectories occur across subsequent gamma cycles nested within each theta cycle, and another in which firing in synchronized gamma discharges without temporal sequences encode a representation of location. We propose that gamma oscillations during theta-phase precession organize the mnemonic recall of population patterns representing places and movement paths. AU - Senior,Timothy J AU - Huxter,John R AU - Allen, Kevin AU - Joseph O'Neill AU - Jozsef Csicsvari ID - 3537 IS - 9 JF - Journal of Neuroscience TI - Gamma oscillatory firing reveals distinct populations of pyramidal cells in the CA1 region of the hippocampus VL - 28 ER - TY - JOUR AB - On the linear track, the recent firing sequences of CA1 place cells recur during sharp wave/ripple patterns (SWRs) in a reverse temporal order [Foster & Wilson (2006) Nature, 440, 680-683]. We have found similar reverse-order reactivation during SWRs in open-field exploration where the firing sequence of cells varied before each SWR. Both the onset times and the firing patterns of cells showed a tendency for reversed sequences during SWRs. These effects were observed for SWRs that occurred during exploration, but not for those during longer immobility periods. Additionally, reverse reactivation was stronger when it was preceded by higher speed (> 5 cm/s) run periods. The trend for reverse-order SWR reactivation was not significantly different in familiar and novel environments, even though SWR-associated firing rates of both pyramidal cells and interneurons were reduced in novel environments as compared with familiar. During exploration-associated SWRs (eSWR) place cells retain place-selective firing [O'Neill et al. (2006) Neuron, 49, 143-155]. Here, we have shown that each cell's firing onset was more delayed and firing probability more reduced during eSWRs the further the rat was from the middle of the cell's place field; that is, cells receiving less momentary place-related excitatory drive fired later during SWR events. However, even controlling for place field distance, the recent firing of cells was still significantly correlated with SWR reactivation sequences. We therefore propose that both place-related drive and the firing history of cells contribute to reverse reactivation during eSWRs. AU - Jozsef Csicsvari AU - Joseph O'Neill AU - Allen, Kevin AU - Senior,Timothy ID - 3523 IS - 3 JF - European Journal of Neuroscience TI - Place-selective firing contributes to the reverse-order reactivation of CA1 pyramidal cells during sharp waves in open-field exploration VL - 26 ER - TY - JOUR AB - We observed sharp wave/ripples (SWR) during exploration within brief (< 2.4 s) interruptions of or during theta oscillations. CA1 network responses of SWRs occurring during exploration (eSWR) and SWRs detected in waking immobility or sleep were similar. However, neuronal activity during eSWR was location dependent, and eSWR-related firing was stronger inside the place field than outside. The eSPW-related firing increase was stronger than the baseline increase inside compared to outside, suggesting a “supralinear” summation of eSWR and place-selective inputs. Pairs of cells with similar place fields and/or correlated firing during exploration showed stronger coactivation during eSWRs and subsequent sleep-SWRs. Sequential activation of place cells was not required for the reactivation of waking co-firing patterns; cell pairs with symmetrical cross-correlations still showed reactivated waking co-firing patterns during sleep-SWRs. We suggest that place-selective firing during eSWRs facilitates initial associations between cells with similar place fields that enable place-related ensemble patterns to recur during subsequent sleep-SWRs. AU - Joseph O'Neill AU - Senior,Timothy AU - Jozsef Csicsvari ID - 3522 IS - 1 JF - Neuron TI - Place-selective firing of CA1 pyramidal cells during sharp wave/ripple network patterns in exploratory behavior VL - 49 ER - TY - JOUR AB - In the hippocampal CA1 area, a relatively homogenous population of pyramidal cells is accompanied by a diversity of GABAergic interneurons. Previously, we found that parvalbumin-expressing basket, axo-axonic, bistratified, and oriens-lacunosum moleculare cells, innervating different domains of pyramidal cells, have distinct firing patterns during network oscillations in vivo. A second family of interneurons, expressing cholecystokinin but not parvalbumin, is known to target the same domains of pyramidal cells as do the parvalbumin cells. To test the temporal activity of these independent and parallel GABAergic inputs, we recorded the precise spike timing of identified cholecystokinin interneurons during hippocampal network oscillations in anesthetized rats and determined their molecular expression profiles and synaptic targets. The cells were cannabinoid receptor type 1 immunopositive. Contrary to the stereotyped firing of parvalbumin interneurons, cholecystokinin-expressing basket and dendrite-innervating cells discharge, on average, with 1.7 ± 2.0 Hz during high-frequency ripple oscillations in an episode-dependent manner. During theta oscillations, cholecystokinin- expressing interneurons fire with 8.8 ± 3.3 Hz at a characteristic time on the ascending phase of theta waves (155 ± 81°), when place cells start firing in freely moving animals. The firing patterns of some interneurons recorded in drug-free behaving rats were similar to cholecystokinin cells in anesthetized animals. Our results demonstrate that cholecystokinin- and parvalbumin-expressing interneurons make different contributions to network oscillations and play distinct roles in different brain states. We suggest that the specific spike timing of cholecystokinin interneurons and their sensitivity to endocannabinoids might contribute to differentiate subgroups of pyramidal cells forming neuronal assemblies, whereas parvalbumin interneurons contribute to synchronizing the entire network. Copyright © 2005 Society for Neuroscience. AU - Klausberger,Thomas AU - Marton,Laszlo F AU - Joseph O'Neill AU - Huck, Jojanneke H AU - Dalezios, Yannis AU - Fuentealba,Pablo AU - Suen, Wai Yee AU - Papp, Edit Cs AU - Kaneko, Takeshi AU - Watanabe, Masahiko AU - Jozsef Csicsvari AU - Somogyi, Péter ID - 3443 IS - 42 JF - Journal of Neuroscience TI - Complementary roles of cholecystokinin- and parvalbumin-expressing GABAergic neurons in hippocampal network oscillations VL - 25 ER -