Browsing by Author "Espinosa, Nelson"

Now showing 1 - 8 of 8
  • Thumbnail Image
    Item
    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
  • Thumbnail Image
    Item
    c-Abl tyrosine kinase down-regulation as target for memory improvement in Alzheimer's disease
    (2023) Leon, Rilda; Gutierrez, Daniela A.; Pinto, Claudio; Morales Acevedo, Cristián Gonzalo; de la Fuente, Catalina; Riquelme, Cristobal; Cortés Castro, Bastián Ignacio; Gonzalez-Martin, Adrian; Chamorro, David; Espinosa, Nelson; Fuentealba Durand, Pablo José; Cancino Lobos, Gonzalo; Zanlungo Matsuhiro, Silvana; Dulcey, Andres E.; Marugan, Juan J.; Rojas, Alejandra Alvarez
    BackgroundGrowing evidence suggests that the non-receptor tyrosine kinase, c-Abl, plays a significant role in the pathogenesis of Alzheimer's disease (AD). Here, we analyzed the effect of c-Abl on the cognitive performance decline of APPSwe/PSEN1 & UDelta;E9 (APP/PS1) mouse model for AD. MethodsWe used the conditional genetic ablation of c-Abl in the brain (c-Abl-KO) and pharmacological treatment with neurotinib, a novel allosteric c-Abl inhibitor with high brain penetrance, imbued in rodent's chow. ResultsWe found that APP/PS1/c-Abl-KO mice and APP/PS1 neurotinib-fed mice had improved performance in hippocampus-dependent tasks. In the object location and Barnes-maze tests, they recognized the displaced object and learned the location of the escape hole faster than APP/PS1 mice. Also, APP/PS1 neurotinib-fed mice required fewer trials to reach the learning criterion in the memory flexibility test. Accordingly, c-Abl absence and inhibition caused fewer amyloid plaques, reduced astrogliosis, and preserved neurons in the hippocampus. DiscussionOur results further validate c-Abl as a target for AD, and the neurotinib, a novel c-Abl inhibitor, as a suitable preclinical candidate for AD therapies.
  • Thumbnail Image
    Item
    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
  • Thumbnail Image
    Item
    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.
  • Thumbnail Image
    Item
    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.
  • Thumbnail Image
    Item
    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.
  • Thumbnail Image
    Item
    Midline thalamic neurons are differentially engaged during hippocampus network oscillations
    (2016) Lara Vásquez, Ariel Fernando; Espinosa, Nelson; Durán, Ernesto; Stockle, Marcelo; Fuentealba, Pablo
  • Thumbnail Image
    Item
    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.