Of Mice and Noise
August 27, 2008 by Kristina Chew, PhD
Filed under Health
BTBR mice are an inbred mouse strain that provide a “mouse model of autism.” BTBR mice are transgenic (their DNA contains an extra human gene thought to be involved in autism) and display “social abnormalities and repetitive behaviors” that correspond to the first and second diagnostic criteria for autism spectrum disorders. A recent study in PLOS One by Maria Luisa Scatton et al. investigates ultrasonic vocalizations in BTBR mice, in order to look at the second diagnostic criterion for ASDs, communication deficits. Scientists separately baby mice of different strains from their mothers and hypothesized that ultrasonic vocalizations might be a measure of social communication in the mice. As The New Scientist notes:
The pups, which had not yet opened their eyes, made noises aimed to bring mom back. These ultrasonic sounds � too low for the human ear to detect � come in 10 different types, from clicking to pure tones.
Most mice in the study used all 10 categories. But the vocabulary of one strain, called BTBR, was limited to four calls, focusing on “harmonics” that contain multiple, simultaneous sounds � like guitar strings plucked together. BTBR mice also called louder and for longer periods of time. “This is similar to what others have found in autistic infants,” says Scattoni.
Via The New Scientist is a clip of the sounds a BTBR mouse makes. A press release also notes this:
The reduced vocal repertoire in BTBR mice may be analogous to atypical vocalizations in some infants and young children later diagnosed with autism. Instead of cooing and babbling, some young children may hum or grunt for extended periods, fail to add inflections into speech patterns, repeat “pop up” words out of context, squeal stereotypically, and laugh inappropriately. Others may be very irritable, cry for long periods of time, and be difficult to console. More crying in these babies may be similar to the higher number of separation calls in BTBR pups.
And, as the authors of the study note, “Mouse pup calls incorporate some properties that suggest they could serve some of the same functions as the crying of human babies, especially their ability to elicit parental retrieval behaviors.”
Never having paid too much attention to repetitive patterns of squeaking in any mouse (like the large gray one that once walked into a glue trap in our old kitchen), I do note certain repeated sounds and frequences in the audio clip of a BTBR mouse vocalizing. But then, I am listening for certain sounds and patterns of sounds.
The “atypical vocalizations” in young children later diagnosed with autism that are considered similar to those of the BTBR mice—humming or grunting “for extended periods, failing to ” inflections into speech patterns,” repetition of “‘pop up’ words out of context”—were features of Charlie’s communication when he was very young, and still can be heard today.It’s noted that researchers hope to use these findings in “identifying genetic and environmental causes of autism, and for evaluating proposed treatments.” But I’m wondering if the study also simply sheds some light about the non-verbal communication of autistic children. We strive constantly to encourage and improve Charlie’s talking, but we’ve also learned to tune in to his non-verbal communication, to his vocalizations. These are often musical, having a melody, rhythm, pitch, tone, phrasing. Charlie’s verbal communication is limited, but he is (and always has been) communicating, and in ways that we need to learn to listen to.
One mouse’s (boy’s) noise is saying something.
There are many mouse models for autism. Prenatal exposure to valproic acid (an anti-convulsant) has been strongly assoicated with autism in humans. Mouse studies have also found that behavioral impairments resembling autism, similar brain damage in the mice are also found in autism autopsy studies.
A new report published last month also replicated those arlier results. A new finding is that male mice are more susceptable to adverse outcomes associated with prenatal exposure to valperoate acid…. there is a 3:1 or 4:1 male female ratio in autism.
http://www.ncbi.nlm.nih.gov/pubmed/18396377?
Two things.
First, with the diagnostic criteria being as variable as they are in humans, I find trying to identify a “mouse model” of autism to be laughable.
Second, Buddy Boy grunted so much when he was born that for some time I thought that he might have sleep apnea, and slept by his bedside with my stethoscope. Like your Charlie, he still grunts (and has his chorus of other unique vocalizations).
Joe
thanks for noting the other study, RAJ—–what would be a “human model” of various mouse diseases…..
Two things, too. One is really not related but just kind of weird: I have a friend who works with singing mice. Very strange.
Second, both TH and Little were MAJOR grunters as infants. All night. Would never stop. And it was GRUNTING…prolonged and loud and we thought it must hurt somehow to do it so much, so gutturally. Very strange.
TH, as I’ve mentioned before, is big on vocalizing, but he doesn’t grunt as much as he squeals, squeaks, says, “eeeeeeeeeeee!” etc. His vocalizations are really all very high pitched.
“thanks for noting the other study, RAJ—–what would be a “human model” of various mouse diseases”
Since there are many ’causes’ of autism (a loosely defined condition) there is likely no one mouse model that would apply to all cases. My interest is in the subgroup associated with an anti-convulsant syndrome since my daughter was exposed in utero to an anti-convulsant.
Prenatal exposure to the anti-convulsant Valproate Acid has been strongly linked to increased risk for autism and the finding has been replicated.
Autism autopsy reports have consistently shown abnormalities in development of the hippocampus and cerebellum and the same finding is also replicated in VPA exposed mice:
http://www.ncbi.nlm.nih.gov/pubmed/18316065?
A recent study has shown that VPA induced ‘autistic’ mice have shown remarkeable improvement with environmental enrichment. Many of the mice have reversed the behavioral impairments through various interventions and that finding can be related to the therapies that have been found to be most effect in the treatment of autism, eg early intervention, speech and language therapy, occupational therapy and if started early enough can reverse to varying degrees the behavioral problems associated with ‘autism’.
Of course, the most important finding related to Fetal Anticonvulsant Syndrome is prevention.
PS I forgot to post the results of the first study that showed the increase risk or ‘autism’ associated with prenatal exposure to Valproate Acid:
http://www.ncbi.nlm.nih.gov/pubmed/16108456?