Speeding of miniature excitatory post-synaptic currents in Ts65Dn cultured hippocampal neurons.
Down syndrome (DS) is the leading non-heritable cause of mental retardation and is due to the effects of an extra chromosome 21. Mouse models of DS have been developed which parallel many of the cognitive and behavioral deficits of DS individuals. Of these, Ts65Dn mice show abnormal hippocampal properties including learning and memory deficits, altered synaptic plasticity and irregular dendritic spines. We assessed synaptic function of cultured postnatal Ts65Dn hippocampal neurons through examination of spontaneous miniature excitatory post-synaptic currents (mEPSCs) and compared them to those from diploid neurons. Averaged amplitudes and frequency of mEPSC events were similar to diploid suggesting presynaptic function is not overtly disrupted in Ts65Dn hippocampal neurons. However, both averaged decay and rise times (10-90% of peak) were significantly faster (approximately 20% for both rise and decay) in Ts65Dn neurons compared to diploid. The distribution of both decay and rise times, indicates global scaling of all percentile groups and is independent of amplitude suggesting normal electrotonic filtering in spite of abnormal expression of GIRK2 channel in Ts65Dn mouse. Western blot analysis suggests overexpression of GluR4 subunit of AMPA receptors which may contribute to faster mEPSC in Ts65Dn neurons. Intrinsic synaptic properties influenced by genetics or epigenetics factors in Ts65Dn postnatal cultured neurons are therefore disrupted and may contribute to the cognitive deficits associated with DS.
Best
Tyler K
TK
Neuroscience Program, USUHS School of Medicine, Bethesda, MD 20814, USA.
Cho-Clark
Madelaine
M
Siarey
Richard J
RJ
Galdzicki
Zygmunt
Z
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000235:genetics / Q000473:pathology; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation / Q000235:genetics; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D011930:Reaction Time / Q000502:physiology / Q000528:radiation effects; D018091:Receptors, AMPA / Q000378:metabolism
D018091:Receptors, AMPA; C104724:glutamate receptor ionotropic, AMPA 4