As CU students well know, learning takes time. Sometimes it may entail incessant reading or repeating a single definition 20 times in a row, but eventually it pays off (at least until after the test). But what if you had to repeat that definition 100 times? 200? 300? Well for those who have Down syndrome this happens to be the case.
Down syndrome (or trisomy 21) is a phenomenon in which a person has 3 copies of the 21st chromosome. This results in a distinct phenotype which includes deficiencies in learning and memory. My youngest sister has Down syndrome, and I know from experience that the most prominent manifestation of slower learning is the need for substantial repetition. I remember spending countless summer hours when I was 11 teaching my sister the ABCs--and not yet comprehending the full implications of Down syndrome I was puzzled at the amount of reiteration necessary. Now studies are finally discovering the biological basis for this detained memory.
In a study published by the Journal of Neuroscience in 2004, researchers from
Standford Medical, Stanford University, and the University of California in San Francisco explored the disparity in learning between Down syndrome and non-syndrome brains. In studying the hippocampus of a genetic mouse model for Down syndrome (Ts65Dn), they discovered that Long Term Potentiation, the predominant mechanism for learning, was suppressed by increased inhibition.
In the study, transverse hippocampal slices of Ts65Dn and of the 2N control mice were studied in various methods. In the first trial, the cells of the dentate gyrus received a tetanus of stimuli. In the 2N mice this resulted in classic LTP as indicated by the significantly elevated post-tetanus synaptic potential. However in the Ts65Dn mice the post-synaptic potential fundamentally remained the same, displaying no significant change to its baseline potential (i.e. no LTP).
A second trial was run with paired pulses which produced a steady no-change PSP in the cells of the 2N mice but yielded a depressed PSP in the Ts65Dn mice, supporting the hypothesis of increased inhibition (not only in magnitude, but as a function of time as well). In the third trial the researchers applied picrotoxin, an inhibitor of GABA receptors, to the dentate gyrus. As a result, LTP was finally induced in the Ts65Dn mice.
The researchers concluded that increased inhibition (either a result of significantly stronger inhibition feedback loops or a greater number of inhibitory synapses) was restraining the depolarization of the post-synaptic membrane, effectively muting NMDA receptors. The picrotoxin facilitated post-synaptic depolarization enough to adequately activate the NMDA receptors, generating LTP.
For decades scientists have made very few inroads into effective treatments for cognitive deficiencies--primarily because the neurological basis has remained a mystery. But with the goal of enhancing memory and focusing the learning capabilities of those with Down syndrome I am confident that these studies will markedly increase our comprehension of how to best teach those with disabilities. In the mean time, the next time you ace a test--thank your LTP.
Kleschevnikov, Alexander et al. "Hippocampal Long-Term Potentiation Supressed by Increased Inhibition in the Ts65Dn Mouse, a Genetic Model of Down Syndrome." The Journal of Neuroscience. 15 September 2004: 8153-8160.