Synaptic deficit in the temporal cortex of partial trisomy 16 (Ts65Dn) mice

Down syndrome results from triplication of human chromosome 21. The distal end of mouse chromosome 16 shares a large region of genetic homology with t he Down syndrome 'critical region' of human chromosome 21. Therefore. a par tially trisomic mouse (Ts65Dn) that possesses a triplication of the distal region of chromosome 16 has been developed as a putative model for Down syn drome. Ts65Dn mice display learning and memory deficits. However, despite t he importance of preserved synaptic integrity for learning and memory, the ultrastructure of neural connectivity has not yet been studied in Ts65Dn mi ce. Therefore, the density and apposition zone length of synapses in the te mporal cortex of aged Ts65Dn mice (n = 4) were compared with those in diplo id controls (n = 4), using quantitative electron microscopy. There were sig nificantly less (30%) asymmetric synapses in the temporal cortex of Ts65Dn mice than in controls (t= -5.067; p = 0.023). However, there was no signifi cant difference between the mean density of symmetric synapses in Ts65Dn mi ce and control mice. In addition, the mean synaptic apposition lengths of b oth asymmetric (15%; t = 9.812, p < 0.0001) and symmetric (11%; t = 5.582; p < 0.0001) synapses were significantly larger in Ts65Dn mice than in contr ols. These results suggest that excitatory synapses are preferentially affe cted in Ts65Dn mice and that there is an attempt to compensate for the defi cit of asymmetric synapses by increasing the contact zone area of existing synapses. The results may also reveal the morphological basis for the learn ing and memory deficits observed in Ts65Dn mice and have a bearing on the c ognitive deficits in Down syndrome in old age. (C) 2000 Published by Elsevi er Science B.V. All rights reserved.