Browsing by Author "Fuentealba, Pablo"

Now showing 1 - 19 of 19
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    Basal Forebrain Gating by Somatostatin Neurons Drives Prefrontal Cortical Activity
    (2019) Espinosa, N.; Alonso, A.; Morales, C.; Espinosa, P.; Chavez, A.E.; Fuentealba, Pablo
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    Basal forebrain somatostatin cells differentially regulate local gamma oscillations and functionally segregate motor and cognitive circuits
    (2019) Espinosa, Nelson; Alonso Imperatore, Carolina Alejandra; Lara Vasquez, Ariel Fernando; Fuentealba, Pablo
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    Brain state-dependent recruitment of high-frequency oscillations in the human hippocampus
    (2017) Billeke, Pablo; Ossandón, Tomás; Stockle, Marcelo; Perrone-Bertolotti, Marcela; Kahane, Philippe; Lachaux, Jean-Philippe; Fuentealba, Pablo
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    Coordinated prefrontal-hippocampal activity and navigation strategy-related prefrontal firing during spatial memory formation
    (2018) Negron-Oyarzo, Ignacio; Espinosa, Nelson; Aguilar, Marcelo; Fuenzalida, Marco; Aboitiz, Francisco; Fuentealba, Pablo
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    Cortical dynamics underlying social behavior in dominance hierarchy and spatial navigation
    (2020) Lara Vásquez, Ariel Fernando; Espinosa, Nelson; Morales, Cristian; Moran, Constanza; Billeke, Pablo; Gallagher, Joseph; Strohl, Joshua J.; Huerta, Patricio T.; Fuentealba, Pablo
    Rodents establish dominance hierarchy as a social ranking system in which one subject acts as dominant over all the other subordinate individuals. Dominance hierarchy regulates food access and mating opportunities, but little is known of its significance in collective behavior, for instance during navigation for foraging or migration. Here, we implemented a simplified goal-directed spatial navigation task in mice and found that the social context exerts significant influence on individual decision-making, even when efficient navigation rules leading to reward had been previously learned. Thus, decision-making and consequent task performance were strongly dependent on contingent social interactions arising during collective navigation, yet their influence on individual behavior was outlined by dominance hierarchy. Dominant animals did not behave as leaders during navigation; conversely, they were most sensitive to social context. Social ranking in turn was reflected in the neural activity and connectivity patterns of the prefrontal cortex and hippocampus, both in anesthetized and behaving mice. These results suggest that the interplay between contingent social interactions and dominance hierarchy can regulate behavioral performance, supported by the intrinsic matrix of coordinated activity in the hippocampal-prefrontal circuit.
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    Dentate Gyrus Somatostatin Cells are Required for Contextual Discrimination during Episodic Memory Encoding
    (2021) Morales Rojas, Cristian Enrique; Morici, Juan Facundo; Espinosa, Nelson; Sacson, Agostina; Lara Vásquez, Ariel Fernando; García Pérez, M. A.; Bekinschtein, Pedro; Weisstaub, Noelia V.; Fuentealba, Pablo
    Memory systems ought to store and discriminate representations of similar experiences in order to efficiently guide future decisions. This problem is solved by pattern separation, implemented in the dentate gyrus (DG) by granule cells to support episodic memory formation. Pattern separation is enabled by tonic inhibitory bombardment generated by multiple GABAergic cell populations that strictly maintain low activity levels in granule cells. Somatostatin-expressing cells are one of those interneuron populations, selectively targeting the distal dendrites of granule cells, where cortical multimodal information reaches the DG. Nonetheless, somatostatin cells have very low connection probability and synaptic efficacy with both granule cells and other interneuron types. Hence, the role of somatostatin cells in DG circuitry, particularly in the context of pattern separation, remains uncertain. Here, by using optogenetic stimulation and behavioral tasks in mice, we demonstrate that somatostatin cells are required for the acquisition of both contextual and spatial overlapping memories.
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    Dominance hierarchy regulates social behavior during spatial movement
    (2024) Lara-Vasquez, Ariel; Espinosa, Nelson; Morales, Cristian; Moran, Constanza; Billeke, Pablo; Gallagher, Joseph; Strohl, Joshua J.; Huerta, Patricio T.; Fuentealba, Pablo
    Copyright © 2024 Lara-Vasquez, Espinosa, Morales, Moran, Billeke, Gallagher, Strohl, Huerta and Fuentealba.Rodents establish dominance hierarchy as a social ranking system in which one subject acts as dominant over all the other subordinate individuals. Dominance hierarchy regulates food access and mating opportunities, but little is known about its significance in other social behaviors, for instance during collective navigation for foraging or migration. Here, we implemented a simplified goal-directed spatial task in mice, in which animals navigated individually or collectively with their littermates foraging for food. We compared between conditions and found that the social condition exerts significant influence on individual displacement patterns, even when efficient navigation rules leading to reward had been previously learned. Thus, movement patterns and consequent task performance were strongly dependent on contingent social interactions arising during collective displacement, yet their influence on individual behavior was determined by dominance hierarchy. Dominant animals did not behave as leaders during collective displacement; conversely, they were most sensitive to the social environment adjusting their performance accordingly. Social ranking in turn was associated with specific spontaneous neural activity patterns in the prefrontal cortex and hippocampus, with dominant mice showing higher firing rates, larger ripple oscillations, and stronger neuronal entrainment by ripples than subordinate animals. Moreover, dominant animals selectively increased their cortical spiking activity during collective movement, while subordinate mice did not modify their firing rates, consistent with dominant animals being more sensitive to the social context. These results suggest that dominance hierarchy influences behavioral performance during contingent social interactions, likely supported by the coordinated activity in the hippocampal-prefrontal circuit.
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    Expression of COUP-TFII Nuclear Receptor in Restricted GABAergic Neuronal Populations in the Adult Rat Hippocampus
    (SOC NEUROSCIENCE, 2010) Fuentealba, Pablo; Klausberger, Thomas; Karayannis, Theofanis; Suen, Wai Yee; Huck, Jojanneke; Tomioka, Ryohei; Rockland, Kathleen; Capogna, Marco; Studer, Michele; Morales, Marisela; Somogyi, Peter
    The COUP-TFII nuclear receptor, also known as NR2F2, is expressed in the developing ventral telencephalon and modulates the tangential migration of a set of subpallial neuronal progenitors during forebrain development. Little information is available about its expression patterns in the adult brain. We have identified the cell populations expressing COUP-TFII and the contribution of some of them to network activity in vivo. Expression of COUP-TFII by hippocampal pyramidal and dentate granule cells, as well as neurons in the neocortex, formed a gradient increasing from undetectable in the dorsal to very strong in the ventral sectors. In the dorsal hippocampal CA1 area, COUP-TFII was restricted to GABAergic interneurons and expressed in several, largely nonoverlapping neuronal populations. Immunoreactivity was present in calretinin-, neuronal nitric oxide synthase-, and reelin-expressing cells, as well as in subsets of cholecystokinin-or calbindin-expressing or radiatum-retrohippocampally projecting GABAergic cells, but not in parvalbumin-and/or somatostatin-expressing interneurons. In vivo recording and juxtacellular labeling of COUP-TFII-expressing cells revealed neurogliaform cells, basket cells in stratum radiatum and tachykinin-expressing radiatum dentate innervating interneurons, identified by their axodendritic distributions. They showed cell type-selective phase-locked firing to the theta rhythm but no activation during sharp wave/ripple oscillations. These basket cells in stratum radiatum and neurogliaform cells fired at the peak of theta oscillations detected extracellularly in stratum pyramidale, unlike previously reported ivy cells, which fired at the trough. The characterization of COUP-TFII-expressing neurons suggests that this developmentally important transcription factor plays cell type-specific role(s) in the adult hippocampus.
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    Hippocampus-cortex communication during sleep
    (2020) Durán Rodríguez, Ernesto Edgardo; Fuentealba, Pablo; Pontificia Universidad Católica de Chile. Facultad de Medicina
    Sleep is critically involved in the formation of long-term memory and is thought to rely on a dialogue between hippocampus and neocortex. The communication between these structures has been proposed to be from the hippocampus to the neocortex. In rodents in the course of sleep, the brain alternates between stages of slow-wave sleep (SWS) and rapid eye movement (REM) sleep. Although sleep stages have been widely investigated, the precise temporal dynamic in hippocampus and cortex has remained largely unresolved. The sleep stages dynamic in hippocampus and cortex might determine the direction of the communication in both areas. Moreover, the hippocampus-cortex communication can be investigated not only in the dynamic of sleep stages, but also restricted to SWS. The interaction between hippocampus and cortex during SWS has been proposed to be top-down regulated by the neocortical slow oscillation (SO) that drives spindles in thalamo-cortical networks and ripples in hippocampal networks. Hippocampal ripples nested in spindles might support the hippocampal-to-neocortical communication. Despite that, these oscillations have been functionally coupled, the temporal association in hippocampus and cortex is not well understood. Furthermore, the thalamus is a central hub that is intimately connected to hippocampus. The thalamus is thought to play an important role in the communication between hippocampus and cortex. However, how thalamic neurons interact with hippocampus is still not clear. Here, we characterized in rats the sleep stages dynamic between neocortex and hippocampus. In addition, we examined the temporal relationships between the specific oscillations during SWS. Lastly, we examined the temporal relationship between thalamic neurons and hippocampal ripples. We simultaneously recorded the electroencephalogram (EEG) from skull electrodes over frontal and parietal cortex and the local field potential (LFP) from the medial prefrontal cortex and dorsal hippocampus (dHC) in order to determine the sleep stage dynamic and the temporal relationship between SOs, spindles and ripples. In addition, we performed simultaneous recordings of thalamic neurons and hippocampal ripples. Our results showed that SWS appeared simultaneously in the hippocampus and the cortex, however REM sleep appeared earlier in the hippocampus. Analysis of the specific oscillations during SWS showed that spindles in the hippocampus are orchestrated by SOs and these spindles modulated hippocampal ripples. Moreover, hippocampal ripples inhibited specifically one class of thalamic neurons. These findings indicated a specific hippocampal-cortex communication, which has clear implications not only for our understanding of the organization of sleep and sleep rhythms, but possibly also for its functions, e.g., in memory formation.
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    Impact of Stress on Gamma Oscillations in the Rat Nucleus Accumbens During Spontaneous Social Interaction
    (2019) Iturra-Mena, A.M.; Aguilar-Rivera, M.; Arriagada-Solimano, M.; Perez-Valenzuela, C.; Fuentealba, Pablo; Dagnino-Subiabre, A.
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    Intrinsic cortical dynamics in the hippocampus-PFC system and social interactions during collective navigation in a decision-making task
    (2020) Lara Vásquez, Ariel Fernando; Fuentealba, Pablo; Pontificia Universidad Católica de Chile. Facultad de Medicina
    Environmental sensory inputs and previously learned information to guide decision-making during complex behaviors such as foraging or navigation. Social mammals forage collectively, yet little is known about the influence of social interactions in decision-making during collective spatial navigation. To achieve efficient decision-making, social animals engaging in collective behavior must balance inherent and contingent factors, yet this process is not well understood. Here, I implemented a simplified spatial navigation task in rodents to assess the role of social interactions and found that they exert a powerful influence on individual decision-making. Indeed, instead of prioritizing memory-based pertinent information, mice shifted their decisions according to contingent social interactions arising during collective navigation. Dominance hierarchy, a form of a social ranking system, was an intrinsic social interaction relevant to organize the timing of behavior during collective navigation. Thus, individual task accuracy was dependent on the density of animals collectively moving during spatial navigation. Finally, dominance hierarchy correlated with brain-state specific coordinated activity expressed as larger hippocampal sharp-wave ripples associated with higher prefrontal firing rates, suggesting reinforced synaptic cortical coupling. These results suggest that both contingent and intrinsic social interactions modulate behavioral performance and are correlated with enhanced activity and connectivity patterns in the hippocampo-prefrontal circuit.
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    Midline thalamic neurons are differentially engaged during hippocampus network oscillations
    (2016) Lara Vásquez, Ariel Fernando; Espinosa, Nelson; Durán, Ernesto; Stockle, Marcelo; Fuentealba, Pablo
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    Prenatal Stress Produces Persistence of Remote Memory and Disrupts Functional Connectivity in the Hippocampal-Prefrontal Cortex Axis
    (2015) Negrón Oyarzo, Ignacio; Neira, David; Espinosa, Nelsón; Fuentealba, Pablo; Aboitiz, Francisco
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    Reactive Disruption of the Hippocampal Neurogenic Niche After Induction of Seizures by Injection of Kainic Acid in the Amygdala
    (2019) Muro García, T.; Martin Suárez, S.; Espinosa, N.; Valcárcel Martin, R.; Marinas, A.; Zaldumbide, L.; Galbarriatu, L.; Sierra, A.; Fuentealba, Pablo; Encinas, J. M.
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    Schizophrenia and reelin: a model based on prenatal stress to study epigenetics, brain development and behavior
    (2016) Negrón Oyarzo, Ignacio; Lara Vásquez, Ariel; Palacios García, Ismael José; Fuentealba, Pablo; Aboitiz, Francisco
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    Sleep-dependent decorrelation of hippocampal spatial representations
    (2024) Valdivia, Gonzalo; Espinosa, Nelson; Lara-Vasquez, Ariel; Caneo, Mauricio; Inostroza, Marion; Born, Jan; Fuentealba, Pablo
    © 2024 The Author(s)Neuronal ensembles are crucial for episodic memory and spatial mapping. Sleep, particularly non-REM (NREM), is vital for memory consolidation, as it triggers plasticity mechanisms through brain oscillations that reactivate neuronal ensembles. Here, we assessed their role in consolidating hippocampal spatial representations during sleep. We recorded hippocampus activity in rats performing a spatial object-place recognition (OPR) memory task, during encoding and retrieval periods, separated by intervening sleep. Successful OPR retrieval correlated with NREM duration, during which cortical oscillations decreased in power and density as well as neuronal spiking, suggesting global downregulation of network excitability. However, neurons encoding specific spatial locations (i.e., place cells) or objects during OPR showed stronger synchrony with brain oscillations compared to non-encoding neurons, and the stability of spatial representations decreased proportionally with NREM duration. Our findings suggest that NREM sleep may promote flexible remapping in hippocampal ensembles, potentially aiding memory consolidation and adaptation to novel spatial contexts.
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    The role of dentate gyrus somatostatin-expressing cells in pattern separation
    (2020) Morales Rojas, Cristian Enrique; Fuentealba, Pablo; Pontificia Universidad Católica de Chile. Facultad de Medicina
    Un paso crítico en la formación de una nueva memoria episódica (memorias sobre nuestras experiencias personales) es garantizar que se almacene de una manera diferente a los recuerdos episódicos similares, previamente adquiridos. La separación de patrones, que es un mecanismo que tiene lugar en el Giro dentado (GD), permitiría la discriminación de recuerdos episódicos similares al aumentar las diferencias de los input sinápticos que llegan a GD. La incapacidad de generar esta discriminación se ha relacionado con el deterioro cognitivo en el envejecimiento, los trastornos neuropsiquiátricos y la epilepsia. Por lo tanto, comprender el mecanismo neuronal de la separación de patrones, que hasta ahora no se conoce bien, tiene importantes beneficios para la salud pública. La regulación de la excitabilidad del GD es crítica, como lo demuestra el deterioro que ocurre en la separación de patrones cuando se induce un aumento artificial de la excitabilidad de GD. Las células que contienen somatostatina (SOM +), un tipo de interneuronas GABAérgica de GD, son buenas candidatas para controlar los inputs excitatorios que alcanzan GD, pero su papel en el control del flujo de información en el circuito de GD sigue siendo difícil de entender. Curiosamente, las evidencias recientes han demostrado un papel importante de SOM + en el control de la excitabilidad DG y en las alteraciones de la memoria, pero su papel directo en la separación de patrones no se ha estudiado. En esta tesis puse a prueba la hipótesis de que se requieren las SOM+ para la discriminación de contextos similares a través del control de la excitabilidad de las células granulares de GD. Para ese propósito, estudié el efecto de la inhibición de SOM + en la excitabilidad de GD en ratones anestesiados. Luego, en un segundo experimento, en ratones despiertos estudié el efecto de la inhibición de SOM + en tareas conductuales que necesitan el mecanismo de separación de patrones. Como quería controlar la actividad de SOM +, sin afectar la actividad de otros miembros de la red neuronal, elegí la optogenética como herramienta metodológica. Esta técnica permite una manipulación selectiva y rápida de la actividad de las SOM +. Descubrí que la supresión optogenética de la actividad de las SOM + modula la velocidad de disparo de un grupo de células que cumplen con los criterios fisiológicos de células glutaminérgicas del GD (cellas granulares y células mossy) y de un grupo de células que cumplen con los criterios fisiológicos de células que contienen Parvalbumin (PV +), un tipo de interneuronas GABAérgica del GD. Además, la estimulación optogenética perjudicó la discriminación contextual y espacial de memorias de reconocimiento similares. Estos resultados sugieren que se requieren las SOM + para una separación de patrones exitosa durante la codificación de memorias episódicas. Indicando que las SOM + deben ser consideradas en futuros modelos del mecanismo de separación de patrones. Específicamente, propongo que las SOM + dirigen una inhibición retrasada.
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    The role of sleep in the organization of spatial representations during memory formation
    (2022) Valdivia Ulloa, Gonzalo; Fuentealba, Pablo; Pontificia Universidad Católica de Chile. Facultad de Medicina
    The study of place cells, discovered by O'Keefe (1971), has focused the spatial representation system in the processes and functions led by the hippocampus. Among these functions, the hippocampus plays a preponderant role in establishing spatial memory, in which sleep is fundamental, suggesting a plausible relationship between sleep and the spatial representations provided by place cells. In this line, there is intense research to establish whether sleep participates in the consolidation and configuration of spatial representations given by place cells and if this is related to spatial memory performance. In this study, we evaluated the influence of sleep on the variations in the configuration of a spatial map given by changes in spatial context during a spatial memory task. Specifically, we first evaluated the influence of sleep on the performance of a spatial memory task, the object in place recognition (OPR), and performed single unit and local field potential recordings in the dorsal CA1 hippocampus in adult rats. Then, we evaluated the influence of sleep and its cardinal oscillations in the configuration of the spatial representations generated by place cells during OPR. Our results show that sleep, specifically non-REM sleep, and its oscillatory patterns (SWRs, spindles, and delta waves), are directly correlated with performance in the OPR memory test. In addition, concerning single-unit recordings, we detected and isolated 612 units. In this line, the detection and classification of individual units were implemented successfully, which was crucial to evaluate the representation system by detecting place cells. We selected units according to their spatial activity, where 41 % were classified as place cells, and the remaining 59 % were classified as non-spatial cells. Also, during post-learning sleep, place cells were highly time-correlated with non-REM oscillatory patterns, like SWRs and spindles. In addition, we evaluated mean firing rate and sparsity during the OPR task showing a general and sleep-independent increase in both parameters after sleep, which is possibly associated with novelty during test. Also, there was a sleep-dependent decrease in mean firing rate during post-learning sleep. Finally, we evaluated the stability of the spatial map on the task through a spatial correlation vector, showing that spatial stability in the novel, but not in the familiar arena zone, decreased associated with a longer duration of post-learning sleep. In conclusion, our results suggest that Non-REM sleep and its oscillations affected spatial representation through the flexibility in the configuration of spatial maps due to changes in the environment. This is also associated with improved spatial memory since instability of place cell spatial configuration is relevant for memory updating during environment exploration.