Some mice show increased synaptic density in specific brain regions, while most models show reduced synaptic density.
NLs play a key role as mediators of synapse formation, as indicated by numerous in vitro studies in which their expression levels were manipulated [ 17, 23, 29, 30, 32, 33], and NL knockout (KO) or autism mutation knock-in (KI) animal models show deficits in synaptic transmission [ 21, 34– 47].
Bottom right image shows synaptic junction.
There is evidence from animal models showing that changes in dendritic morphology, probably associated with synaptic disturbances, correlate with alterations in memory and learning abilities [26], [27].
In addition, the DS brains and Dyrk1A overdosage models showed selective changes in the transcripts composition of neuroligin mRNAs as well as reductions in the "synaptic" acetylcholinesterase variant AChE-S mRNA and corresponding increases in the stress-inducible AChE-R mRNA variant, yielding key synaptic proteins with unusual features.
In addition to suggesting a new type of experiment and providing testable predictions, our model shows how conclusions regarding synaptic arithmetic can be influenced by an array of seemingly innocuous experimental design choices.
The model shows how the experimentally observed increase in the dendritic density of Ih and IA could have a major role in constraining the temporal integration window for the main CA1 synaptic inputs.
In a transgenic mouse model, Cummings et al. show that synaptic changes occur shortly after soluble amyloid-β levels become measurable, and before the rapid increases in total Aβ and Aβ42 Aβ40 that lead to detectable plaque deposition.
Additionally, other AD mouse models have shown GABAergic interneuron and synaptic plasticity deficits in the dentate gyrus [ 15, 17, 47, 48].
