A similar impairment in CA3 mossy fibre LTP in the R6/2 mouse model of Huntington's disease and in the complexin II knockout mouse.
Complexin II is reduced in Huntington's disease (HD) patients and in the R6/2 mouse model of HD. Mice lacking complexin II (Cplx2-/- mice) show selective cognitive deficits that reflect those seen in R6/2 mice. To determine whether or not there is a common mechanism that might underlie the cognitive deficits, long-term potentiation (LTP) was examined in the CA3 region of hippocampal slices from R6/2 mice and Cplx2-/- mice. While associational/commissural (A/C) LTP was not significantly different, mossy fibre (MF) LTP was significantly reduced in slices from R6/2 mice and Cplx2-/- mice compared with wild-type (WT) and Cplx2+/+ control mice. MF field excitatory postsynaptic potentials (fEPSPs) in response to paired stimuli were not significantly different between control mice and R6/2 or Cplx2-/- mice, suggesting that MF basal glutamate release is unaffected. Forskolin (30 microm) caused an increase in glutamate release at MF synapses in slices from R6/2 mice and from Cplx2-/- mice that was not significantly different from that seen in control mice, indicating that the capacity for increased glutamate release is not diminished. Thus, R6/2 mice and Cplx2-/- mice have a common selective impairment of MF LTP in the CA3 region. Together, these data suggest that complexin II is required for MF LTP, and that depletion of complexin II causes a selective impairment in MF LTP in the CA3 region. This impairment in MF LTP could contribute to spatial learning deficits observed in R6/2 and Cplx2-/- mice.
Gibson
Helen E
HE
Department of Anatomy, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Reim
Kerstin
K
Brose
Nils
N
Morton
A Jennifer
AJ
Jones
Susan
S
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D033942:Adaptor Proteins, Vesicular Transport; D000367:Age Factors; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003521:Cyclopropanes / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology / Q000528:radiation effects; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000473:pathology*; D006816:Huntington Disease / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000503:physiopathology* / Q000528:radiation effects; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D013997:Time Factors
D033942:Adaptor Proteins, Vesicular Transport; D000927:Anticonvulsants; D003521:Cyclopropanes; D018691:Excitatory Amino Acid Antagonists; D009419:Nerve Tissue Proteins; C095993:complexin II; C082313:2-(2,3-dicarboxycyclopropyl)glycine; D005576:Colforsin; D015763:2-Amino-5-phosphonovalerate; D005998:Glycine