Quentin S Fischer, Ph.D.
The adult brain is capable of considerable functional reorganization often manifest as long term modification of synaptic strength (strengthening as long-term potentiation or LTP, and weakening as long term depression or LTD). This plasticity is increasingly targeted in rehabilitative therapeutic interventions in attempts to restore brain function after mild traumatic brain injury (mTBI). In particular, recovery of function after brain injury has involved training regimens thought to work by repetitively activating and thus enhancing synaptic efficacy or the passive and active stimulation of afferent pathways and their synaptic targets by noninvasive or chronically implanted stimulating apparatus. However, the stimulation protocols generally used in clinical rehabilitation strategies are based on those used in classic in vitro animal studies, often focusing on the frequency of conditioning synaptic stimulation but with little attention paid to the pattern of stimulation. Most stimulation protocols for inducing LTP and LTD have relied on regular stimulation patterns where interstimulus intervals (ISIs) are all equal (coefficient of variation, CV=0). However, some recent studies have incorporated more physiologically salient stimulation patterns (e.g. Poisson-distributed ISIs, CV=1). The major goal of my research is to determine the stimulation patterns that are most effective at facilitating the functional reorganization of synapses after mTBI. My pre-clinical laboratory animal based experiments will systematically test how patterns of synaptic stimulation activate calcium signaling and trigger plasticity (LTD and LTP) under normal conditions and after mTBI. These results will provide baseline data in the normal brain and insights into how mTBI modulates sensitivity to potentially restorative therapeutic post-injury neural stimulation interventions. These results should provide quantitative characterization of the interactions of stimulation pattern and frequency, indicating where appropriate intersections of these two features of stimulation of surviving cortical pathways can be defined, enabling the design of optimal stimulus sets to facilitate the selective strengthening and weakening of appropriate cortical pathways in injured cerebral cortex. This knowledge should guide the future application of stimulus based neurorehabilitation therapies that use emerging clinical in vivo stimulation technologies such as magnetic stimulation, optical stimulation, or multielectrode array stimulation in the injured human brain.
Fischer QS, Aleem S, Zhou H, Pham TA. (2007). Adult visual experience promotes recovery of primary visual cortex from long-term monocular deprivation. Learn Mem 14: 573-80.
Fischer QS, Graves A, Evans S, Lickey ME, Pham TA. (2007). Monocular deprivation in adult mice alters visual acuity and single-unit activity. Learn Mem 14: 277-86.
McGee AW, Yang Y, Fischer QS, Daw NW, Strittmatter SM. (2005). Experience-driven plasticity of visual cortex limited by myelin and Nogo receptor. Science 309: 2222-6.
Yang Y, Fischer QS, Zhang Y, Baumgärtel K, Mansuy IM, Daw NW. (2005). Reversible block of experience-dependent plasticity by calcineurin in mouse visual cortex. Nat. Neuroscie 8(6): 791-6.
Daw N, Rao Y, Wang XF, Fischer Q, Yang Y. (2004). LTP and LTD vary with layer in rodent visual cortex. Vision Res 44: 3377-80.
Fischer QS, Beaver CJ, Yang Y, Rao Y, Jakobsdottir KB, Storm DR, McKnight GS, Daw NW. (2004). Requirement for the RIIbeta isoform of PKA, but not calcium-stimulated adenylyl cyclase, in visual cortical plasticity. J Neurosci 24: 9049-58.
Rao Y, Fischer QS, Yang Y, McKnight GS, LaRue A, Daw NW. (2004). Reduced ocular dominance plasticity and long-term potentiation in the developing visual cortex of protein kinase A RII alpha mutant mice. Eur J Neurosci 20(3): 837-42.
Shimegi S, Fischer QS, Yang Y, Sato H, Daw NW. (2003). Blockade of cyclic AMP-dependent protein kinase does not prevent the reverse ocular dominance shift in kitten visual cortex. J Neurophysiol 90(6): 4027-32.
Beaver CJ, Fischer QS, Ji Q, Daw NW. (2002). Orientation selectivity is reduced by monocular deprivation in combination with PKA inhibitors. J Neurophysiol 88(4): 1933-40.
Rowe MH, Fischer Q. (2001). Dynamic properties of retino-geniculate synapses in the cat. Vis Neurosci 18(2): 219-31.
Beaver CJ1, Ji Q, Fischer QS, Daw NW. (2001). Cyclic AMP-dependent protein kinase mediates ocular dominance shifts in cat visual cortex. Nat Neurosci 4(2): 159-63.
Fischer QS1, Kirby MA. (1991). Number and distribution of retinal ganglion cells in anubis baboons (Papio anubis). Brain Behav Evol 37(4): 189-203.
- Ph.D. in Psychology (Neuroscience program), University of California, Riverside CA
Thesis: The Role of Binocular Interactions in the Development of Mammalian Retinocollicular Topography
- Master of Arts in Psychology (Neuroscience program), University of California, Riverside CA
Thesis: The Role of Cell Death in Sculpting Retinal Ganglion Cell Topography and Patterns of Central Projection
- Bachelor of Arts in Psychology (Behavioral Neuroscience program), University of Colorado, Boulder CO
- Instructor, Baylor College of Medicine, Department of Neuroscience, Houston, TX
- Instructor, Baylor College of Medicine, Department of Psychiatry & Behavioral Sciences, Houston, TX
- Postdoctoral Associate, Yale University Medical School, Dept. Ophthalmology & Visual Science, New Haven CT
- Postdoctoral Research Associate, Ohio University, Department of Biological Sciences, Neurobiology Program, Athens, OH
- Graduate Student, University of California, Departments of Psychology and Neuroscience, Riverside CA
- Professional Research Associate II, University of Colorado, Department of Psychology, Boulder, CO
- Research Assistant, University of Colorado, Department of Psychology, Boulder, CO
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