Biological Psychology, 7e

Animation 17.1 Brain Explorer[Click image to open in browser.]

1Animation 17.2 AMPA and NMDA Receptors

Video 17.3 (1) Morris Water Maze: Non-transgenic (Normal) Mouse Trials

These videos show performances on the Morris hidden-platform water maze by a normal mouse (Non-transgenic) and a mouse genetically engineered to provide a model for Alzheimers disease (PDAPP). The Morris water maze (WM) was devised in 1981 by British neuroscientist Richard G. M. Morris, and it has proved useful in studying many aspects of brain function and learning behavior. Originally devised for research with rats, the WM is also used with other rodents. The subject is placed in a circular tank of opaque fluid and swims until it finds a small platform just below the surface. On successive trials, normal animals find the platform more and more rapidly, relying on landmarks placed on the walls around the maze. Note that on successive trials, the mouse is started from different positions along the perimeter, so it must learn the location of the platform rather than learning a particular route to find it.The three Non-transgenic trials show that a normal mouse learns the location of the platform rapidly. The three PDAPP videos show the impaired performance of a mouse genetically engineered to overexpress human mutant amyloid precursor protein (APP) in the nervous system, called a platelet-derived amyloid precursor protein (PDAPP) mouse. The PDAPP mouse does not show a regular decrease in time required to reach the hidden platform on successive trials; it seems to find the platform only by chance. Richard Morris reports that the initial idea for the water maze came in the 1970s when he observed the firing of hippocampal place cells in John OKeefes laboratory in London. After moving to the University of St. Andrews, Morris decided to test further whether rats could respond to an abstract sense of location in a familiar environment, rather than to specific sensory cues. Morriss laboratory was initially housed in the marine laboratory, and he speculates that seeing fish in tanks every day may have suggested the idea of making rats swim to a target hidden underwater. He found that normal rats were very successful at this (Morris, 1981). Lesions of the hippocampus prevented good performance in the WM. To determine whether the lesions really affected spatial navigation rather than disrupting sensory processing, swimming, or motivation, Morris and collaborators added a task in which the top of the platform was raised just above the surface of the water; rats with hippocampal lesions succeeded at this task, although they failed with the hidden platform (Morris, Garrud, Rawlins, and OKeefe, 1982). Morriss group later found that an antagonist of NMDA (see text pp.536-538) disrupted hippocampal-dependent learning without affecting other kinds of learning (Morris, Anderson, Lynch, and Baudry, 1986). The WM has since been used for a variety of studies, including research on neocortical functioning, aging, effects of brain transplants, and neuropharmacological studies. In the research from which the videos were taken, mice, after having reached criterion with the target in one location, have to learn a new location of the target. This spatial discrimination reversal procedure is especially difficult for PDAPP mice (Chen et al., 2000).ReferencesChen, G., Chen, K. S., Knox, J., Inglis, J. et al. (2000). A learning deficit related to age and beta-amyloid plaques in a mouse model of Alzheimers disease. Nature, 408 (6815), 975-979.Morris, R. G. M. (1981). Spatial localization does not require the presence of local cues. Learning and Motivation, 12, 239-260.Morris, R. G. M., Anderson, E., Lynch, G. S. and Baudry, M. (1986). Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5. Nature, 319 (6056), 774-776.Morris, R. G. M., Garrud, P., Rawlins, J. N., and OKeefe, J. (1982). Place navigation impaired in rats with hippocampal lesions. Nature, 297 (5868), 631-633.(Courtesy of Stephen Martin and Richard Morris, University of Edinburgh, Department of Neuroscience. )3Video 17.3 (2) Morris Water Maze: Transgenic (PDAPP) Mouse Trails

These videos show performances on the Morris hidden-platform water maze by a normal mouse (Non-transgenic) and a mouse genetically engineered to provide a model for Alzheimers disease (PDAPP). The Morris water maze (WM) was devised in 1981 by British neuroscientist Richard G. M. Morris, and it has proved useful in studying many aspects of brain function and learning behavior. Originally devised for research with rats, the WM is also used with other rodents. The subject is placed in a circular tank of opaque fluid and swims until it finds a small platform just below the surface. On successive trials, normal animals find the platform more and more rapidly, relying on landmarks placed on the walls around the maze. Note that on successive trials, the mouse is started from different positions along the perimeter, so it must learn the location of the platform rather than learning a particular route to find it.The three Non-transgenic trials show that a normal mouse learns the location of the platform rapidly. The three PDAPP videos show the impaired performance of a mouse genetically engineered to overexpress human mutant amyloid precursor protein (APP) in the nervous system, called a platelet-derived amyloid precursor protein (PDAPP) mouse. The PDAPP mouse does not show a regular decrease in time required to reach the hidden platform on successive trials; it seems to find the platform only by chance. Richard Morris reports that the initial idea for the water maze came in the 1970s when he observed the firing of hippocampal place cells in John OKeefes laboratory in London. After moving to the University of St. Andrews, Morris decided to test further whether rats could respond to an abstract sense of location in a familiar environment, rather than to specific sensory cues. Morriss laboratory was initially housed in the marine laboratory, and he speculates that seeing fish in tanks every day may have suggested the idea of making rats swim to a target hidden underwater. He found that normal rats were very successful at this (Morris, 1981). Lesions of the hippocampus prevented good performance in the WM. To determine whether the lesions really affected spatial navigation rather than disrupting sensory processing, swimming, or motivation, Morris and collaborators added a task in which the top of the platform was raised just above the surface of the water; rats with hippocampal lesions succeeded at this task, although they failed with the hidden platform (Morris, Garrud, Rawlins, and OKeefe, 1982). Morriss group later found that an antagonist of NMDA (see text pp.536-538) disrupted hippocampal-dependent learning without affecting other kinds of learning (Morris, Anderson, Lynch, and Baudry, 1986). The WM has since been used for a variety of studies, including research on neocortical functioning, aging, effects of brain transplants, and neuropharmacological studies. In the research from which the videos were taken, mice, after having reached criterion with the target in one location, have to learn a new location of the target. This spatial discrimination reversal procedure is especially difficult for PDAPP mice (Chen et al., 2000).ReferencesChen, G., Chen, K. S., Knox, J., Inglis, J. et al. (2000). A learning deficit related to age and beta-amyloid plaques in a mouse model of Alzheimers disease. Nature, 408 (6815), 975-979.Morris, R. G. M. (1981). Spatial localization does not require the presence of local cues. Learning and Motivation, 12, 239-260.Morris, R. G. M., Anderson, E., Lynch, G. S. and Baudry, M. (1986). Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5. Nature, 319 (6056), 774-776.Morris, R. G. M., Garrud, P., Rawlins, J. N., and OKeefe, J. (1982). Place navigation impaired in rats with hippocampal lesions. Nature, 297 (5868), 631-633.(Courtesy of Stephen Martin and Richard Morris, University of Edinburgh, Department of Neuroscience. )4