How Do You Make a Rain Mouse?
February 14, 2008 by Kristina Chew, PhD
Filed under Health
MIT researchers have found that the lack of a brain protein, Shank 1, in mice causes them to learn some tasks faster but, when tested weeks later, they were not able to retain that knowledge. Shank 1 is a key protein in building synapses, and mutations in the closely related protein, Shank 3, have been linked to autism. The mice were found to be able to learn a spatial task quickly but (as compared to normal mice) were later unable to remember how to do it. The study is published in the Journal of Neuroscience; here are more details form Science Blog:
…… mice genetically engineered to lack a key protein used for building synapses–the junctions through which brain cells communicate–actually learned a spatial memory task faster and better than normal mice. But when tested weeks later, they couldn’t remember what they had learned as well as normal mice, and they had trouble remembering contexts that should have provoked fear.
“These opposite effects on different types of learning are reminiscent of the mixed features of autistic patients, who may be disabled in some cognitive areas but show enhanced abilities in others,” said Albert Y. Hung, a postdoctoral associate at the Picower Institute, staff neurologist at Massachusetts General Hospital and co-author of the study. “The superior learning ability of these mutant mice in a specific realm is reminiscent of human autistic savants.”
Hung said that while it seems counter-intuitive that loss of an important synaptic scaffold protein would result in improved learning among the mice in this study, the absence of this protein may “trap” the mice’s synapses in a more plastic state, which means the synapses are ready to respond to input but not maintain it in long-term memory.
Aberrant synapse development and faulty structure of dendritic spines–tiny protrusions on the surface of neurons that receive messages from other neurons–are often associated with neurodevelopmental disorders, including autism, in humans.
The enhanced spatial learning of the genetically engineered mice is similar to that of mice who are engineered to have a mutation in another protein, neuroligin3, which is associated with autism and which binds directly to Shank 1.
The researchers suggest that the mice who have been genetically engineered not to have the Shank 1 protein are like autistic savants who (like the character, Raymond, in the movie Rain Man and Daniel Tammet, the author of Born on a Blue Day) have special, specific abilities, such as being able to recite prime number after prime number or to draw the city of Rome with photographic precision. While the mutant mice could learn certain tasks quickly, the researchers noted that they did not retain this knowledge, while autistic persons with savant abilities seem to often have these abilities and, in some cases, do these same things over and over.
On the other hand, I’ve often seen my son learn some new skill—such as saying a new sounds—on his first or second try, and then take months (years, for some sounds, like /l/) to be able to make the sound again and under his own volition. Might the MIT researchers’ findings be more generally applied to how autistic persons learn?
SHANK3 defects have been found in ASD subjects but also in people with mental retardation without an ASD diagnosis. The failure of genetic research in autism is its inability to control for the confounding variable of mental retardation associated with autism type features.
http://www.ncbi.nlm.nih.gov/pubmed/16284256?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
In 1965 Leo Kanner, the clinician who first recognized autism as a distinct neuropsychiatric disorder voiced his objection to the 1960’s ‘epidemic’ of autism when mentally retarded children with bizarre behaviors who shared one or more part features of the syndrome of autism were given the fashionable label of ‘autism’.
The current vastly expanded definition and criteria used to confer a diagnosis are vague, ambigous and subjective. This likely explains the second autism epidemic and also explains why such diverse children as Fragile X mentally retarded boys, brain damaged children, language delayed children people with personality disorders and even Romanian orphans who were institutionalized as infants and suffered severe emotional deprivation, abuse and neglect can all meet diagnostic criteria for an ASD.
My son has never been diagnosed with mental retardation, though—based on his cognitive performance and school work and minimal language—I think this would have been his diagnosis in the past.
No epidemic of autism, 1st or 2nd……
The thing that makes savants savants is their prodigious long term memories. One explanation behind their ability to do calendar calculating is that they look at calendars over an extended period of time and absorb or learn or whatever the pattern so that they can apply it to future and past dates.
Savants who learn to play music don’t forget songs that they learn. Savants that memorize stuff don’t turn around and forget it all, if they did why would anyone ever make a fuss over their skill?
These mice look more like a mouse model for amnesia. But typically, anyone who thinks they have a thing that can get funded as autism research will bend it that way because whereas there’s little money for “amnesia” research there’s plenty for autism research because of all the bizarros howling about a fake autism epidemic.
“In 1965 Leo Kanner, the clinician who first recognized autism as a distinct neuropsychiatric disorder voiced his objection to the 1960’s ‘epidemic’ of autism when mentally retarded children with bizarre behaviors who shared one or more part features of the syndrome of autism were given the fashionable label of ‘autism’.”
RAJ, you’ve mentioned that a couple of times. I’m intrigued; where could I find/what’s the citation for that? I’d like to read it first-hand. Thanks.
I agree with Ms Clark. This bears little even superficial resemblance to autism or savant abilities. I see it as funding motivated analogies.
Interesting stuff.
Regan;
Regarding your question about Leo Kanners observation about the over diagnosing of autism. The article was published in 1965 in Behavioral Science. I found the entire article on a website and am posting the link for you:
http://neurodiversity.com/library_kanner_1965.html
This sage advice was not heeded by many authors. While the majority of the Europeans were satisfied with a sharp delineation of infantile autism as an illness sui generis, there was a tendency in this country to view it as a developmental anomaly ascribed exclusively to maternal emotional determinants. Moreover, it became a habit to dilute the original concept of infantile autism by diagnosing it in many disparate conditions which show one or another isolated symptom found as a part feature of the overall syndrome. Almost overnight, the country seemed to be populated by a multitude of autistic children, and somehow this trend became noticeable overseas as well. Mentally defective children who displayed bizarre behavior were promptly labeled autistic and, in accordance with preconceived notions, both parents were urged to undergo protracted psychotherapy in addition to treatment directed toward the defective child’s own supposedly underlying emotional problem.
Kristina wrote:
“My son has never been diagnosed with mental retardation, though—based on his cognitive performance and school work and minimal language—I think this would have been his diagnosis in the past.
No epidemic of autism, 1st or 2nd……”
I agree with you that there is no epidemic of autism, neither in the early 1960’s or after the introduction of DSM-III-R, ICD-10, ADOS-R, ARI-R and other ‘Gold Standard’ instruments to diagnose an ASD.
All of these Gold Standard diagnostic tools have included an ever expanding checklist of autistic ’symptoms’ in a Chinese menu fashion, one from column A, two from Column B…
The core problem is that isolated features which are a featured part of the overall syndrome of autism but are not specific to autism are all given equal weight under these diagnostic schemes and what Kanner called the ’sui generis’ of the core defining feature of autism has been lost, leading to the myth of the autism epidemic just as it did in the early 1960’s.
The best evidence is the data produced by the Autism Genome Consortium this year alone. The entire concept of the Consortium is flawed, they look at only the minority of children with a specific genetic anomaly that meet criteria for an ASD, and cannot see (because of the design flaw) the majority of cases who do not meet the criteria for an ASD and are excluded from the studies leading to false assumptions and misleading conclusions.
Every single finding published this year (SHANK3, Neuroligins etc.) have all been previously reported in patient populations with a variety of neurological conditions, primarily mental retardation, but not autism. In every single case the Consortium has promoted as an ‘autism’ gene, the phenotype is actually mental retardation with a minority presenting with enough nonspecific autistic features to qualify for an ASD diagnosis.
RAJ,
Thank you very much for taking the time to find the full text of the Kanner paper. Much appreciated. It’s helpful to be able and put this into a historical framework.