Browsing by Author "Espinosa, Nelson"
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- 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
- Itemc-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 AlvarezBackgroundGrowing 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.
- Itemc-Abl tyrosine kinase down-regulation as target for memory improvement in Alzheimer's disease(Wiley, 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 AlvarezBackgroundGrowing 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.
- 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.
- ItemMidline thalamic neurons are differentially engaged during hippocampus network oscillations(2016) Lara Vásquez, Ariel Fernando; Espinosa, Nelson; Durán, Ernesto; Stockle, Marcelo; Fuentealba, Pablo