(Joint Appointment with Psychiatry)
Offices: Natural Sciences Centre 234/
Robarts Research Institute 3228
p. 519.661.3452 x. 83452/
519.931-5777 x. 83452
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.
Bekinschtein, P., Kent, B.A., Oomen, C.A., Clemenson, G.D., Gage, F.H., Saksida, L.M. & Bussey, T.J. (2013) BDNF in the dentate gyrus is required for consolidation of "pattern-separated" memories. Cell Reports, 5: 759-768. PMCID: PMC3898274
In one of the first papers to investigate the molecular basis of pattern separation we used a new and improved test to demonstrate that BDNF acts on an as-needed basis in the encoding/storage/consolidation, but not the retrieval, stage of pattern-separated memory formation.
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.
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
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}
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
Nithianantharajah, J, Komiyama N.H., McKechanie, A., Johnstone, M., Blackwood D.H., St Clair, D., Emes R.D., van de Lagemaat L.N., Saksida L.M., Bussey T.J. * & Grant, S.G.N. * (2013) Synaptic scaffold evolution generated components of vertebrate cognitive complexity, Nature Neuroscience, 16 (1): 16-24.
We tested both mice and humans with deletion mutations in the family of Dlg proteins—which are implicated in many diseases including schizophrenia— on touchscreen-based tests tapping into the same cognitive domains, and found that mice and humans with deletion mutations showed strikingly similar cognitive profiles.
Graybeal, C., Feyder, M., Schulman, E., Saksida, L.M., Bussey, T.J., Brigman, J.L. & Holmes, A. (2011) Moderate stress or prefrontal damage facilitates reversal learning: rescue by prefrontal-infused BDNF. Nature Neuroscience, 14(12):1507-9. Recommended by Faculty of 1000 as “Must Read”, see www.facultyof1000.com.
Creer, D., Romberg C., Saksida L.M., van Praag, H., Bussey T.J. (2010) Running enhances spatial pattern separation in mice. Proc Natl Acad Sci U S A 107(5):2367-72.
Clelland C.D., Choi M., Romberg C., Clemenson G.D. Jr., Tyers P., Jessberger S., Saksida L.M., Barker R.A., Gage F.H., Bussey T.J. (2009) A functional role for adult hippocampal neurogenesis in spatial pattern separation. Science, 325 (5937): 210-213. Recommended by Faculty of 1000 as “Must Read”, see www.facultyof1000.com. Featured as a “Research Highlight” in Nature Reviews Neuroscience 10: 622 - 623 (2009).
This paper provided the first evidence that adult-born neurons in the dentate gyrus may be necessary for pattern separation. Mice with ablated neurogenesis were impaired on both touchscreen and hand-testing tasks when stimuli were presented with little spatial separation, but not when stimuli were more widely separated in space.
Bartko, S.J., Winters, B.D., Cowell, R., Saksida, L.M., & Bussey, T.J. (2007). Perceptual impairments following perirhinal cortex lesions in rats: zero-delay object recognition and simultaneous oddity discriminations. Journal of Neuroscience, 27(10), 2548-2559.
Winters, B.D., Saksida, L.M., & Bussey, T.J. (2006). Paradoxical facilitation of object recognition memory following infusion of scopolamine into perirhinal cortex: implications for cholinergic system function. Journal of Neuroscience, 26, 9520-9529.
Winters, B.D., & Bussey, T.J. (2005). Transient inactivation of perirhinal cortex disrupts encoding, retrieval, and consolidation of object recognition memory. Journal of Neuroscience, 25:52-61.
Winters, B.D., & Bussey, T.J. (2005). Glutamate receptors in perirhinal cortex mediate encoding, retrieval, and consolidation of object recognition memory. Journal of Neuroscience, 25:4243-4251.
Winters, B. D., Forwood, S. E., Cowell, R. A., Saksida, L. M., & Bussey, T. J. (2004). Double dissociation between the effects of peri-postrhinal cortex and hippocampal lesions on tests of object recognition and spatial memory: Heterogeneity of function within the temporal lobe. Journal of Neuroscience, 24, 5901-5908.
Here we demonstrated the first functional double dissociation between the hippocampus and peri+postrhinal cortex in a single experiment. These results provide strong evidence in favour of heterogeneity and independence of function within the temporal lobe, and against the prevailing medial temporal lobe memory system view.
Bussey, T. J., Saksida, L.M. and Murray, E.A. (2002). Perirhinal cortex resolves feature ambiguity in complex visual discriminations. European Journal of Neuroscience 15: 365-74.
The first experimental paper testing predictions of the Bussey & Saksida (2002) computational model of the representational-hierarchical view. Experiments confirmed the predictions of the computational simulations, but were not consistent with the predictions of alternative views.
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.
The first publication of a complex, touchscreen-based cognitive test for mice. This introduced the possibility of testing mice on object learning and memory tasks similar to those used with rats, monkeys, and humans, paving the way both for improved translation as well as the comprehensive behavioural assessment of transgenic and gene-knockout models.
Murray, E.A. & Bussey, T.J. (1999). Perceptual-mnemonic functions of perirhinal cortex. Trends in Cognitive Sciences, 3: 142-151 (invited article). For Commentary on this paper, see Simons et al. (2003) Trends in Cognitive Sciences, 3:248-249.
The first presentation of the ‘perceptual-mnemonic’ view of perirhinal cortex, which argued, in contrast to the prevailing medial temporal lobe memory system view, that the functional effects of lesions in perirhinal cortex on visual discrimination learning and memory may best be understood by considering the the underlying stimulus representations rather than assuming that ‘perceptual' and ‘mnemonic' functions are neatly organized into anatomically segregated modules in the brain.
Bussey, T.J., Muir, J.L. & Aggleton, J.P. (1999). Functionally dissociating aspects of event memory: The effects of combined perirhinal and postrhinal cortex lesions on object and place memory in the rat. Journal of Neuroscience, 19: 495-502. Demonstrated dissociations between object recognition and place learning, and provided evidence of differential hippocampal and perirhinal cortex function.
Demonstrated lesion-based dissociations between object recognition and place learning. This provided a strong challenge to the prevailing medial temporal lobe memory system view.
Bussey, T.J., Warburton, E.C., Aggleton, J.P. & Muir, J.L. (1998). Fornix lesions can facilitate acquisition of the transverse patterning task: A challenge for “configural” theories of hippocampal function. Journal of Neuroscience, 18: 1622-1631.
Bussey, T.J., Muir, J.L., Everitt, B.J. & Robbins, T.W. (1997). Triple dissociation of anterior cingulate, posterior cingulate, and medial frontal cortices on visual discrimination tasks using a touchscreen testing procedure for the rat. Behavioral Neuroscience, 111: 920-936.
Bussey, T.J., Muir, J.L. & Robbins, T.W. (1994). A novel automated touchscreen procedure for assessing learning in the rat using computer graphic stimuli. Neuroscience Research Communications, 15: 103-110.
The first publication of a rodent touchscreen-based system for cognitive assessment, showing that it was indeed possible to train rats to use a touchscreen.