Deficits in hippocampal CA1 LTP induced by TBS but not HFS in the Ts65Dn mouse: a model of Down syndrome.
Down syndrome (DS) is the most common genetically defined cause of intellectual disabilities. Both hippocampal function and volume seem to be disproportionally reduced in individuals with DS and in at least one aneuploid murine model of DS, the Ts65Dn mouse. Two previous studies by one research group have reported deficits in long-term potentiation (LTP) induced by in vitro high-frequency stimulation (HFS) of hippocampal CA1 synapses of adult Ts65Dn mice. Here, we report on the results of our own investigation on LTP in Ts65Dn mice. This study was designed to confirm the previous findings and possibly shed some light onto potential mechanisms underlying the reported deficit in this important form of long-term synaptic plasticity in a mouse model of DS. LTP was induced in area CA1 with either theta burst stimulation (TBS) or HFS. Contrary to the previous reports, our results showed no significant difference in HFS-induced LTP between Ts65Dn and euploid littermate mice. We have found, however, a significant reduction of the amount of TBS-induced LTP in Ts65Dn mice compared to euploid controls. Because this specific LTP deficit can be rescued by bath application of picrotoxin (10 microM), we hypothesize that an increase in GABA(A)-mediated inhibition or in plasticity of the inhibitory circuitry in Ts65Dn mice may underlie the observed deficits. However, future experiments to examine the state of hippocampus CA1 GABAergic inhibition in Ts65Dn mice will be necessary to further explore these hypotheses.
Costa
Alberto C S
AC
Eleanor Roosevelt Institute, University of Denver, 1899 Gaylord Street, Denver, CO 80206, USA. acosta@du.edu
Grybko
Michael J
MJ
D000818:Animals; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000503:physiopathology*; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D009924:Organ Culture Techniques; D010852:Picrotoxin / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D018756:GABA Antagonists; D010852:Picrotoxin