Lisa Saksida
Professor
(Joint Appointment with Psychology)
Office: Natural Sciences Centre 233/
Robarts Research Institute 3228
p. 519.661.3604 x. 83604/
519.931.5777 x. 83604
e. tcnlab@robarts.ca
I'm interested in cognition (how the healthy brain does it, what goes wrong in neurodegenerative and neuropsychiatric disease, and identifying targets for therapy) as well as improving preclinical-to-clinical translation.
Selected Publications:
Horner, A.E., Heath, C.J., Hvoslef-Eide, M., Kent, B.A., Kim, C.H., Nilsson, S., Alsiö, J., Oomen, C.A., Holmes, A., Saksida, L.M., & Bussey, T.J. (2013) The touchscreen operant platform for testing learning and memory in rats and mice. Nature Protocols, 8(10):1961-84. PMCID: PMC3914026
Oomen, C.A., Hvoslef-Eide, M., Heath, C.J., Mar, A.C., Horner, A.E., Bussey, T.J., & Saksida, L.M. (2013) The touchscreen operant platform for testing working memory and pattern separation in rats and mice. Nature Protocols, 8(10):2006-21. PMCID: PMC3982138
Mar, A.C., Horner, A.E., Nilsson, S., Alsiö, J., Kent, B.A., Kim, C.H., Holmes, A., Saksida, L.M., & Bussey, T.J. (2013) The touchscreen operant platform for assessing executive function in rats and mice. Nature Protocols, 8(10):1985-2005.
Due to the increasingly popularity of our touchscreen platform, Nature Protocols asked us to submit 3 manuscripts providing detailed protocols and advice about how best to use them. Tests of learning, memory, working memory, pattern separation and executive function are described.
Brigman J.L., Daut, R. Wright, T., Gunduz-Cinar, O., Graybeal, C., Jiang, Z., Saksida, L.M., Jinde, S., Pease, M., Bussey, T.J., Lovinger, D.M., Nakazawa, K., & Holmes, A. (2013) GluN2B in corticostriatal circuits governs choice learning and choice shifting. Nature Neuroscience, 16(8):1101-10. PMC3725191
Romberg,C., Yang, S., Melani, R., Andrews, M.R., Horner, A.E., Spillantini, M.G., Bussey, T.J., Fawcett, J.W., Pizzorusso, T. & Saksida, L.M. (2013) . Depletion of perineuronal nets enhances recognition memory and long-term depression in the perirhinal cortex. Journal of Neuroscience, 33 (16): 7057-7065. PMCID: PMC3655688
Ryan, T.J., Kopanitsa, M.V., Indersmitten, T., Nithianantharajah, J., Afinowi, N.O., Pettit, C., Stanford, L.E., Sprengel, R., Saksida, L.M., Bussey T.J., O’Dell, T.J., Grant, S.G.N., and Komiyama, N.H. (2013) Genetic exchange of evolutionarily derived GluN2A and GluN2B cytoplasmic domains identifies shared and unique contributions to vertebrate behavior and synaptic plasticity, Nature Neuroscience, 16(1): 25-32. PMCID: PMC3979286
Barense, M.D., Groen, I.I.A., Lee, A.C.H., Yeung, L-K, Brady, S.M., Gregori, M., Kapur, N., Bussey, T.J., Saksida, L.M.* & Henson, R.N.A.* (2012). Intact memory for irrelevant information impairs perception in amnesia. Neuron, 75(1):157-167. PMC3657172 *These authors contributed equally. See Preview in Neuron by M. Baxter 75(1):8-10.
Using a perceptual matching task, we showed that amnesics with damage in perirhinal cortex were vulnerable to object-based perceptual interference. This supports our representational-hierarchical model, and challenges prevailing conceptions of amnesia, suggesting that effects of damage to specific medial temporal lobe regions are better understood not in terms of damage to a dedicated declarative memory system, but in terms of impoverished representations of the stimuli those regions maintain.
Romberg, C., McTighe, S.M., Heath, C.J., Whitcomb, D., Cho, K., Bussey, T.J. & Saksida, L.M. (2012) False recognition in a mouse model of Alzheimer’s disease: rescue with sensory restriction and memantine. Brain, 135:2103-2114. PMC3381719
We showed that the tgCRND8 (amyloid) mouse model of Alzheimer’s disease (AD) exhibits false recognition, and that this can be rescued with memantine or sensory restriction. This provides a compelling potential mechanism for false recognition seen in AD and in patients with mild cognitive impairment.
Romberg C., Mattson. M.P., Mughal, M.R., Bussey T.J., Saksida L.M. (2011). Attentional impairments in the triple transgenic mouse model of Alzheimer’s disease: Rescue with donepezil (Aricept). Journal of Neuroscience, 31, 3500-3507. PMC3066152
Here we adapted a test of attention to the touchscreen and showed that the 3xTgAD mouse model of AD, like patients on the same touchscreen task, shows a sustained vigilance deficit that is rescued by an anticholinersterase (the approved AD treatment donepezil [Aricept]). This indicates high face and predictive validity for the task, and utility for translational research into AD.
McTighe, S.M., Cowell, R.C., Winters, B.D., Bussey, T.J. & Saksida, L.M. (2010). Paradoxical false memory for objects after brain damage. Science, 330 (6009): 1408-10. See commentary in Science by H. Eichenbaum 330: 1331 - 1332 (2010). Recommended by Faculty of 1000 as “Must Read”, see www.facultyof1000.com. Free full text
Here we found, as predicted by our representational-hierarchical view, that recognition memory impairment may be due, not to treating familiar experiences as being novel, but instead to novel items being experienced as familiar. This impairment was rescued via a sensory restriction procedure that reduces interference, providing strong support for our model.
Cowell, R., Bussey, T.J. & Saksida, L.M. (2010). Components of recognition memory: dissociable cognitive processes or just differences in representational complexity? Hippocampus, 20(11):1245-62.
Cowell, R., Bussey, T.J. & Saksida, L.M. (2010). Functional dissociations within the ventral object processing pathway: cognitive modules or a hierarchical continuum? Journal of Cognitive Neuroscience, 22(11):2460-79
This is an extension of the Bussey & Saksida (2002) model of the representational-hierarchical view, in which we demonstrate that the differential effects of lesions in ventral visual stream on visual discrimination may be due to compromised representations within a hierarchical representational continuum rather than the commonly assumed impairment in a specific type of learning, memory, or perception.
Murray, E.A., Bussey, T.J. & Saksida, L.M. (2007). Visual perception and memory: A revised view of medial temporal lobe function in primates and rodents. Annual Review of Neuroscience, 30, 99-122.
Saksida, L.M., Bussey, T. J., Buckmaster, C. A. & Murray, E.A. (2007). Impairment and facilitation of transverse patterning after lesions of the perirhinal cortex and hippocampus, respectively. Cerebral Cortex, 17, 108-115.
We showed that monkeys with perirhinal cortex lesions were impaired, whereas monkeys with selective hippocampal lesions were improved, on acquisition of the transverse-patterning task. This striking double dissociation provides strong evidence against the view that perirhinal cortex and hippocampus are functionally unitary, and consistent with the representational-hierarchical view.
Cowell, R.C., Bussey, T.J., & Saksida, L.M. (2006). Why does brain damage impair memory? A connectionist model of object recognition memory in perirhinal cortex. Journal of Neuroscience, 26, 12186-97.
This is an extension of the Bussey & Saksida (2002) model, which shows that it is possible to use a representational-hierarchical framework to account not just for visual discrimination impairments, but also for object recognition impairments, after damage to perirhinal cortex. This model made the prediction that damage to perirhinal cortex should lead to false recognition, which we confirmed in McTighe et al. (Science, 2010).
Morton, A.J., Skillings, E., Bussey, T.J. & Saksida, L.M. (2006). Measuring cognitive deficits in disabled mice using an automated interactive touchscreen system. Nature Methods, 3, 767. Awarded the "highly commended" prize in the NC3Rs 3Rs competition, 2008.
The concomitant appearance of motor disability and cognitive deficits is very common in neurodegenerative disease; however there are few cognitive tests suitable for animals with motor impairments. We showed that our automated touchscreen-based cognitive testing system could pick up on cognitive impairments that were not secondary to motor impairments, and that motor-impaired mice can perform well in this apparatus.
Graham, K.S., Scahill, V. L., Hornberger, M., Barense, M.D., Lee, A.C.H., Bussey, T.J. & Saksida, L.M. (2006). Abnormal categorization and perceptual learning in patients with hippocampal damage. Journal of Neuroscience, 26, 7547-54.
Barense, M.D., Bussey, T.J., Lee, A.C.H., Rogers, T.T., Davies, R.R., Saksida, L.M., Murray, E.A., & Graham, K.S. (2005). Functional specialization in the human medial temporal lobe. Journal of Neuroscience, 25, 10239-46.
Bussey, T. J. and Saksida, L.M. (2002). The organization of visual object representations: a connectionist model of effects of lesions in perirhinal cortex. European Journal of Neuroscience 15: 355-64. (Authorship in alphabetical order: both authors contributed equally.)
The first computational model of the representational-hierarchical view. Simulations using this model have generated numerous predictions that we and others have tested experimentally in mice, rats, monkeys and humans.
Bussey, T.J., Saksida, L.M. & Rothblat, L.A. (2001). Discrimination of computer-graphic stimuli by mice: A method for the behavioral characterization of transgenic and gene-knockout models. Behavioral Neuroscience, 115: 957-960.
