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Your search keyword '"Saksida, Lisa M."' showing total 236 results
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236 results on '"Saksida, Lisa M."'

4. Stress-inducible phosphoprotein 1 (HOP/STI1/STIP1) regulates the accumulation and toxicity of α-synuclein in vivo

Author

Lackie, Rachel E., de Miranda, Aline S., Lim, Mei Peng, Novikov, Vladislav, Madrer, Nimrod, Karunatilleke, Nadun C., Rutledge, Benjamin S., Tullo, Stephanie, Brickenden, Anne, Maitland, Matthew E. R., Greenberg, David, Gallino, Daniel, Luo, Wen, Attaran, Anoosha, Shlaifer, Irina, Del Cid Pellitero, Esther, Schild-Poulter, Caroline, Durcan, Thomas M., Fon, Edward A., Duennwald, Martin, Beraldo, Flavio H., Chakravarty, M. Mallar, Bussey, Timothy J., Saksida, Lisa M., Soreq, Hermona, Choy, Wing-Yiu, Prado, Vania F., and Prado, Marco A. M.

Published
2022
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6. Dlk1 dosage regulates hippocampal neurogenesis and cognition

Author

Montalbán-Loro, Raquel, Lassi, Glenda, Lozano-Ureña, Anna, Perez-Villalba, Ana, Jiménez-Villalba, Esteban, Charalambous, Marika, Vallortigara, Giorgio, Horner, Alexa E., Saksida, Lisa M., Bussey, Timothy J., Trejo, José Luis, Tucci, Valter, Ferguson-Smith, Anne C., and Ferrón, Sacri R.

Published
2021

7. Neuroanatomical and cognitive biomarkers of alpha‐synuclein propagation in a mouse model of synucleinopathy prior to onset of motor symptoms.

Author

Tullo, Stephanie, Miranda, Aline S., del Cid‐Pellitero, Esther, Lim, Mei Peng, Gallino, Daniel, Attaran, Anoosha, Patel, Raihaan, Novikov, Vladislav, Park, Megan, Beraldo, Flavio H., Luo, Wen, Shlaifer, Irina, Durcan, Thomas M., Bussey, Timothy J., Saksida, Lisa M., Fon, Edward A., Prado, Vania F., Prado, Marco A. M., and Chakravarty, M. Mallar

Subjects
PARKINSON'S disease, MAGNETIC resonance imaging, CELLULAR pathology, LABORATORY mice, ANIMAL disease models
Abstract

Significant evidence suggests that misfolded alpha‐synuclein (aSyn), a major component of Lewy bodies, propagates in a prion‐like manner contributing to disease progression in Parkinson's disease (PD) and other synucleinopathies. In fact, timed inoculation of M83 hemizygous mice with recombinant human aSyn preformed fibrils (PFF) has shown symptomatic deficits after substantial spreading of pathogenic alpha‐synuclein, as detected by markers for the phosphorylation of S129 of aSyn. However, whether accumulated toxicity impact human‐relevant cognitive and structural neuroanatomical measures is not fully understood. Here we performed a single unilateral striatal PFF injection in M83 hemizygous mice, and using two assays with translational potential, ex vivo magnetic resonance imaging (MRI) and touchscreen testing, we examined the combined neuroanatomical and behavioral impact of aSyn propagation. In PFF‐injected mice, we observed widespread atrophy in bilateral regions that project to or receive input from the injection site using MRI. We also identified early deficits in reversal learning prior to the emergence of motor symptoms. Our findings highlight a network of regions with related cellular correlates of pathology that follow the progression of aSyn spreading, and that affect brain areas relevant for reversal learning. Our experiments suggest that M83 hemizygous mice injected with human PFF provides a model to understand how misfolded aSyn affects human‐relevant pre‐clinical measures and suggest that these pre‐clinical biomarkers could be used to detect early toxicity of aSyn and provide better translational measures between mice and human disease. [ABSTRACT FROM AUTHOR]

Published
2024
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11. An optimized acetylcholine sensor for monitoring in vivo cholinergic activity

Author

Jing, Miao, Li, Yuexuan, Zeng, Jianzhi, Huang, Pengcheng, Skirzewski, Miguel, Kljakic, Ornela, Peng, Wanling, Qian, Tongrui, Tan, Ke, Zou, Jing, Trinh, Simon, Wu, Runlong, Zhang, Shichen, Pan, Sunlei, Hires, Samuel A., Xu, Min, Li, Haohong, Saksida, Lisa M., Prado, Vania F., Bussey, Timothy J., Prado, Marco A. M., Chen, Liangyi, Cheng, Heping, and Li, Yulong

Published
2020
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13. Sex‐dependent cholinergic effects on amyloid pathology: A translational study.

Author

German‐Castelan, Liliana, Shanks, Hayley R. C., Gros, Robert, Saito, Takashi, Saido, Takaomi C., Saksida, Lisa M., Bussey, Timothy J., Prado, Marco A. M., Schmitz, Taylor W., and Prado, Vania F.

Abstract

INTRODUCTION: About two‐thirds of Alzheimer's Disease (AD) patients are women, who exhibit more severe pathology and cognitive decline than men. Whether biological sex causally modulates the relationship between cholinergic signaling and amyloid pathology remains unknown. METHODS: We quantified amyloid beta (Aβ) in male and female App‐mutant mice with either decreased or increased cholinergic tone and examined the impact of ovariectomy and estradiol replacement in this relationship. We also investigated longitudinal changes in basal forebrain (cholinergic function) and Aβ in elderly individuals. RESULTS: We show a causal relationship between cholinergic tone and amyloid pathology in males and ovariectomized female mice, which is decoupled in ovary‐intact and ovariectomized females receiving estradiol. In elderly humans, cholinergic loss exacerbates Aβ. DISCUSSION: Our findings emphasize the importance of reflecting human menopause in mouse models. They also support a role for therapies targeting estradiol and cholinergic signaling to reduce Aβ. Highlights: Cholinergic tone regulates amyloid beta (Aβ) pathology in males and ovariectomized female mice.Estradiol uncouples the relationship between cholinergic tone and Aβ.In elderly humans, cholinergic loss correlates with increased Aβ in both sexes. [ABSTRACT FROM AUTHOR]

Published
2024
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20. TDP-43 gains function due to perturbed autoregulation in a Tardbp knock-in mouse model of ALS-FTD

Author

White, Matthew A., Kim, Eosu, Duffy, Amanda, Adalbert, Robert, Phillips, Benjamin U., Peters, Owen M., Stephenson, Jodie, Yang, Sujeong, Massenzio, Francesca, Lin, Ziqiang, Andrews, Simon, Segonds-Pichon, Anne, Metterville, Jake, Saksida, Lisa M., Mead, Richard, Ribchester, Richard R, Barhomi, Youssef, Serre, Thomas, Coleman, Michael P., Fallon, Justin R., Bussey, Timothy J., Brown, Jr, Robert H., and Sreedharan, Jemeen

Published
2018
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30. Functional Dissociations within the Ventral Object Processing Pathway: Cognitive Modules or a Hierarchical Continuum?

Author

Cowell, Rosemary A., Bussey, Timothy J., and Saksida, Lisa M.

Abstract

We examined the organization and function of the ventral object processing pathway. The prevailing theoretical approach in this field holds that the ventral object processing stream has a modular organization, in which visual perception is carried out in posterior regions and visual memory is carried out, independently, in the anterior temporal lobe. In contrast, recent work has argued against this modular framework, favoring instead a continuous, hierarchical account of cognitive processing in these regions. We join the latter group and illustrate our view with simulations from a computational model that extends the perceptual-mnemonic feature-conjunction model of visual discrimination proposed by Bussey and Saksida [Bussey, T. J., & Saksida, L. M. "The organization of visual object representations: A connectionist model of effects of lesions in perirhinal cortex." "European Journal of Neuroscience, 15," 355-364, 2002]. We use the extended model to revisit early data from Iwai and Mishkin [Iwai, E., & Mishkin, M. "Two visual foci in the temporal lobe of monkeys." In N. Yoshii & N. Buchwald (Eds.), "Neurophysiological basis of learning and behavior" (pp. 1-11). Japan: Osaka University Press, 1968]; this seminal study was interpreted as evidence for the modularity of visual perception and visual memory. The model accounts for a double dissociation in monkeys' visual discrimination performance following lesions to different regions of the ventral visual stream. This double dissociation is frequently cited as evidence for separate systems for perception and memory. However, the model provides a parsimonious, mechanistic, single-system account of the double dissociation data. We propose that the effects of lesions in ventral visual stream on visual discrimination are due to compromised representations within a hierarchical representational continuum rather than impairment in a specific type of learning, memory, or perception. We argue that consideration of the nature of stimulus representations and their processing in cortex is a more fruitful approach than attempting to map cognition onto functional modules.

Published
2010
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31. Implications of Animal Object Memory Research for Human Amnesia

Author

Winters, Boyer D., Saksida, Lisa M., and Bussey, Timothy J.

Abstract

Damage to structures in the human medial temporal lobe causes severe memory impairment. Animal object recognition tests gained prominence from attempts to model "global" human medial temporal lobe amnesia, such as that observed in patient HM. These tasks, such as delayed nonmatching-to-sample and spontaneous object recognition, for assessing object memory in non-human primates and rodents have proved invaluable as animal models of specific aspects of human declarative memory processes. This paper reviews research in non-human primates and rats using object recognition memory tasks to assess the neurobiological bases of amnesia. A survey of this research reveals several important implications for our understanding of the anatomical basis of memory and the medial temporal lobe amnesic syndrome. First, research with monkeys and rats reveals that the contributions of medial temporal lobe structures such as the hippocampus and perirhinal cortex to memory processes are dissociable, with particular structures contributing to specific tasks on the basis of the specific type of information that a structure is optimized to process. Second, the literature suggests that cognitive tasks requiring integration of different types of information, such as in the case of complex, multimodal declarative memory, will recruit structures of the medial temporal lobe in an interactive manner. The heterogeneity of function within the medial temporal lobe, as well as the multimodal and complex nature of human declarative memory, implies that animal tests of object recognition memory, once believed to be comprehensive models for the study of human global amnesia, model just one important facet of human declarative memory. Finally, in light of the research reviewed here, it is apparent that the specific nature of amnesia observed in an individual with medial temporal lobe damage will depend on the particular medial temporal lobe regions affected and their specific representational capacities.

Published
2010
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34. Impaired Discrimination Learning in Mice Lacking the NMDA Receptor NR2A Subunit

Author

Brigman, Jonathan L., Feyder, Michael, and Saksida, Lisa M.

Abstract

N-Methyl-D-aspartate receptors (NMDARs) mediate certain forms of synaptic plasticity and learning. We used a touchscreen system to assess NR2A subunit knockout mice (KO) for (1) pairwise visual discrimination and reversal learning and (2) acquisition and extinction of an instrumental response requiring no pairwise discrimination. NR2A KO mice exhibited significantly retarded discrimination learning. Performance on reversal was impaired in NR2A KO mice during the learning phase of the task; with no evidence of heightened perseverative responses. Acquisition and extinction of an instrumental behavior requiring no pairwise discrimination was normal in NR2A KO mice. The present findings demonstrate a significant and selective deficit in discrimination learning following loss of NR2A.

Published
2008
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