Browsing by Author "Fuentealba, Pablo"
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- ItemBasal Forebrain Gating by Somatostatin Neurons Drives Prefrontal Cortical Activity(2019) Espinosa, N.; Alonso, A.; Morales, C.; Espinosa, P.; Chavez, A.E.; Fuentealba, Pablo
- ItemBasal 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
- ItemBrain 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
- ItemCoordinated 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
- ItemCortical 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, PabloRodents 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.
- ItemDentate 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, PabloMemory 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.
- ItemDominance 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, PabloCopyright © 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.
- ItemDynamics of Action Potential Initiation in the GABAergic Thalamic Reticular Nucleus In Vivo(2012) Munoz, Fabian; Fuentealba, PabloUnderstanding the neural mechanisms of action potential generation is critical to establish the way neural circuits generate and coordinate activity. Accordingly, we investigated the dynamics of action potential initiation in the GABAergic thalamic reticular nucleus (TRN) using in vivo intracellular recordings in cats in order to preserve anatomically-intact axo-dendritic distributions and naturally-occurring spatiotemporal patterns of synaptic activity in this structure that regulates the thalamic relay to neocortex. We found a wide operational range of voltage thresholds for action potentials, mostly due to intrinsic voltage-gated conductances and not synaptic activity driven by network oscillations. Varying levels of synchronous synaptic inputs produced fast rates of membrane potential depolarization preceding the action potential onset that were associated with lower thresholds and increased excitability, consistent with TRN neurons performing as coincidence detectors. On the other hand the presence of action potentials preceding any given spike was associated with more depolarized thresholds. The phase-plane trajectory of the action potential showed somato-dendritic propagation, but no obvious axon initial segment component, prominent in other neuronal classes and allegedly responsible for the high onset speed. Overall, our results suggest that TRN neurons could flexibly integrate synaptic inputs to discharge action potentials over wide voltage ranges, and perform as coincidence detectors and temporal integrators, supported by a dynamic action potential threshold.
- ItemExpression 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, PeterThe 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.
- ItemHippocampus-cortex communication during sleep(2020) Durán Rodríguez, Ernesto Edgardo; Fuentealba, Pablo; Pontificia Universidad Católica de Chile. Facultad de MedicinaSleep 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.
- ItemHuman Anterior Insula Encodes Performance Feedback and Relays Prediction Error to the Medial Prefrontal Cortex(2020) Billeke, Pablo; Ossandon, Tomas; Perrone-Bertolotti, Marcela; Kahane, Philippe; Bastin, Julien; Jerbi, Karim; Lachaux, Jean-Philippe; Fuentealba, PabloAdaptive behavior requires the comparison of outcome predictions with actual outcomes (e.g., performance feedback). This process of performance monitoring is computed by a distributed brain network comprising the medial prefrontal cortex (mPFC) and the anterior insular cortex (AIC). Despite being consistently co-activated during different tasks, the precise neuronal computations of each region and their interactions remain elusive. In order to assess the neural mechanism by which the AIC processes performance feedback, we recorded AIC electrophysiological activity in humans. We found that the AIC beta oscillations amplitude is modulated by the probability of performance feedback valence (positive or negative) given the context (task and condition difficulty). Furthermore, the valence of feedback was encoded by delta waves phase-modulating the power of beta oscillations. Finally, connectivity and causal analysis showed that beta oscillations relay feedback information signals to the mPFC. These results reveal that structured oscillatory activity in the anterior insula encodes performance feedback information, thus coordinating brain circuits related to reward-based learning.
- ItemImpact 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.
- ItemImpaired Functional Connectivity in the Prefrontal Cortex: A Mechanism for Chronic Stress-Induced Neuropsychiatric Disorders(2016) Negron Oyarzo, Ignacio; Aboitiz, Francisco; Fuentealba, Pablo
- ItemIntrinsic 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 MedicinaEnvironmental 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.
- ItemKetamine-Treatment During Late Adolescence Impairs Inhibitory Synaptic Transmission in the Prefrontal Cortex and Working Memory in Adult Rats(2019) Angel Perez, Miguel; Morales, Camila; Santander, Odra; Garcia, Francisca; Gomez, Isabel; Penaloza-Sancho, Valentin; Fuentealba, Pablo; Dagnino-Subiabre, Alexies; Moya, Pablo R.; Fuenzalida, MarcoSchizophrenia (SZ) is associated with changes in the structure and function of several brain areas. Several findings suggest that these impairments are related to a dysfunction in gamma-aminobutyric acid (GABA) neurotransmission in brain areas such as the medial prefrontal cortex (mPFC), the hippocampus (HPC) and the primary auditory cortex (A1); however, it is still unclear how the GABAergic system is disrupted in these brain areas. Here, we examined the effect of ketamine (Ket) administration during late adolescence in rats on inhibition in the mPFC-, ventral HPC (vHPC), and A1. We observe that Ket treatment reduced the expression of the calcium-binding protein parvalbumin (PV) and the GABA-producing enzyme glutamic acid decarboxylase 67 (GAD67) as well as decreased inhibitory synaptic efficacy in the mPFC. In addition, Ket- treated rats performed worse in executive tasks that depend on the integrity and proper functioning of the mPFC. Conversely, we do not find such changes in vHPC or A1. Together, our results provide strong experimental support for the hypothesis that during adolescence, the function of the mPFC is more susceptible than that of HPC or A1 to NMDAR hypofunction, showing apparent structure specificity. Thus, the impairment of inhibitory circuitry in mPFC could be a convergent primary site of SZ-like behavior during the adulthood.
- ItemMidline thalamic neurons are differentially engaged during hippocampus network oscillations(2016) Lara Vásquez, Ariel Fernando; Espinosa, Nelson; Durán, Ernesto; Stockle, Marcelo; Fuentealba, Pablo
- ItemOptogenetic Suppression of Lateral Septum Somatostatin Neurons Enhances Hippocampus Cholinergic Theta Oscillations and Local Synchrony(2023) Espinosa, Nelson; Alonso, Alejandra; Caneo, Mauricio; Moran, Constanza; Fuentealba, PabloThe septal complex regulates both motivated and innate behaviors, chiefly by the action of its diverse population of long-range projection neurons. A small population of somatostatin-expressing GABAergic cells in the lateral septum projects deep into subcortical regions, yet on its way it also targets neighboring medial septum neurons that profusely innervate cortical targets by ascending synaptic pathways. Here, we used optogenetic stimulation and extracellular recordings in acutely anesthetized transgenic mice to show that lateral septum somatostatin neurons can disinhibit the cholinergic septo-hippocampal pathway, thus enhancing the amplitude and synchrony of theta oscillations while depressing sharp-wave ripple episodes in the dorsal hippocampus. These results suggest that septal somatostatin cells can recruit ascending cholinergic pathways to promote hippocampal theta oscillations.
- ItemPrenatal 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
- ItemReactive 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.
- ItemSchizophrenia 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