News & Views Archives
Issue No. 8, Fall 2006
October is National Down Syndrome Awareness Month. Buddy Walks will take place all over the country. To find a Buddy Walk in your community, please check the official Buddy Walk web site.
In July 2006, the Lucile Packard Children's Hospital at Stanford opened a clinic dedicated to the evaluation and treatment of children with Down syndrome. The demand for this clinic has been high and we are currently placing interested families on a wait list. To accommodate patient demand, we are in the process of expanding the number of patients who can be seen in the clinic. The Down Syndrome Clinic is open to children < 18 years old from the Northern and Central California & Northern Nevada region. Families that have attended the clinic have provided positive feedback and have been impressed with our services. We are working hard to expand our capacity and request your patience during this time. For more information regarding the clinic, please visit our clinic web page.
We are pleased to inform you of ongoing work carried out by our research collaborator Dr. L. Jacobs at the University of California at Berkeley. Dr. Jacobs has created a special maze with which researchers can test spatial memory in a Down syndrome mouse model.
News from our collaborator Dr. Jacobs at UC Berkeley
By Drs. Jacobs and Heyn
Dr. Jacobs and her colleagues are comparative psychologists, who specialize in how rodents learn, particularly about space. In the past, they have studied not only laboratory mice and humans, but also wild tree squirrels, voles and kangaroo rats. In all of these mammals, spatial learning is done by the hippocampus, a large structure in the brain. The hippocampus is especially important for navigation and orientation in space. Current work from the Jacobs lab is showing how females and males (wild kangaroo rats, domestic lab mice and humans) orient differently: females are better at recalling the location of specific objects, while males have a better sense of direction. This gender difference is reflected in the size and structure of their hippocampi: the greater sense of direction is correlated with an increased number of brain cells in a specific area of the hippocampus called the dentate gyrus (1).
How does this relate to Down syndrome? In Down syndrome, damage to the hippocampus contributes to cognitive impairment. It turns out that people with Down syndrome have spatial memory deficits on laboratory tasks that mimic spatial mazes developed for laboratory rodents (2). Dr. Jacobs is interested in finding out how exactly spatial memory is impaired in people with Down syndrome. To pursue this question, researchers in Dr. Jacobs’ lab are collecting data on spatial tests performed by the Ts65Dn mouse—a well-established mouse model for Down syndrome (For a review of Ts65Dn mice, please see News & Views Issue No.2).
Spatial memory of Ts65Dn and normal control mice is tested in a unique maze that was created by Dr. Jacobs (See Figure 1.). Mice are trained to navigate through this maze using surrounding objects in the room as guidance cues, such as plastic or foam blocks of different shapes or artificial flowers attached outside the maze. Researchers measure how long it takes the mice to find a hidden exit behind which they find a reward. Navigation time is measured under various conditions. For example, all guidance cues present or all cues removed or the cues close by or far away removed.
Research results so far suggest that the Ts65Dn mice are impaired in these spatial tests compared to normal mice: The Ts65Dn mice seem to memorize routes, while their control littermates encode the maze as an object in a map of the room. So when guidance cues outside the maze are removed, the Ts65Dn mice run their memorized route, while the control mice slow down and look around before making their choices.
A similar impairment was found in children with Down syndrome whose spatial memory was tested in a virtual maze analogous to the one used for the Ts65Dn mice (2). These children spent significantly less time looking for a hidden object in the right place compared to age matched children without Down syndrome (2).
How can these results be interpreted? According to one theory postulated by Dr. Jacobs, the hippocampus divides spatial memory into two functions that help us move in space: a "memory for object locations" and a "sense of direction." Knowing or recalling that a certain office is located on a certain street in your city is an example of “memory for objects in different locations.” Not remembering where the office is found, but having a sense of which direction you need to head to reach a certain city neighborhood represents an example of a “sense of direction.” In other words, it is the difference between having a local map that shows all the buildings in your immediate neighborhood versus not recognizing the buildings, but having a compass in your head and knowing that you need to head north. Having a sense of direction is related to understanding the larger context—where you are in space and perhaps the social context of your location.
Research results to date have shown that Ts65Dn and control mice differ in how they use these two ways of moving in space. Ts65Dn mice look at the world differently, remember cues differently and navigate through space differently. Scientists in Dr. Jacobs’ laboratory are collaborating with researchers at the Stanford Down Syndrome Center to find out why and how Ts65Dn mice move through space in a different way compared to normal mice. Work from researchers in Dr. Mobley’s laboratory suggests that certain communication circuits in the hippocampus that are involved in “direction finding” and “context encoding” are damaged over time in Ts65Dn mice. In collaboration with scientists in Dr. Mobley’s laboratory, Dr Jacobs and colleagues have found that different behaviors on the spatial maze are correlated with the expression of certain genes that are triplicated in the Ts65Dn mice.
Future work will focus on refining experiments on the spatial maze to find more specific behavioral and cognitive differences between Ts65Dn mice and normal mice. It will be particularly important to determine how behavior and cognitive abilities are related to gene expression in different parts of the hippocampus. Identifying the differences in behavior and gene expression in Ts65Dn mice will help determine which gene(s) are responsible for spatial memory deficits in mice and ultimately humans with Down syndrome.
Jacobs, LF and Schenk, F (2003) Unpacking the cognitive map: the parallel map theory of hippocampal function. Psychological Review. 110:285-315.
Pennington, BF, Moon, J, Edgin, J, Stedron, J, and Nadel, L (2003) The neuropsychology of Down syndrome: evidence for hippocampal dysfunction. Child Dev. 74:75-93.